diff --git a/python/samples/04-hosting/container/hyperlight_codeact/Dockerfile b/python/samples/04-hosting/container/hyperlight_codeact/Dockerfile
index 218ba87b8ba..00faccb8ff7 100644
--- a/python/samples/04-hosting/container/hyperlight_codeact/Dockerfile
+++ b/python/samples/04-hosting/container/hyperlight_codeact/Dockerfile
@@ -7,6 +7,8 @@
 #     python/
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 # Copy the in-tree agent-framework packages we need. Order matters for editable
diff --git a/python/samples/04-hosting/container/hyperlight_codeact/README.md b/python/samples/04-hosting/container/hyperlight_codeact/README.md
index 44c9a53e918..7d6e8a04614 100644
--- a/python/samples/04-hosting/container/hyperlight_codeact/README.md
+++ b/python/samples/04-hosting/container/hyperlight_codeact/README.md
@@ -68,6 +68,12 @@ Follow the instructions in the
 [Running the Agent Host Locally](../../foundry-hosted-agents//README.md#running-the-agent-host-locally)
 section of the README in the Foundry Hosted Agent directory.
 
+The image and hosted deployment definitions set `PYTHONNOUSERSITE=1`; see the
+[Python startup configuration](../../foundry-hosted-agents/README.md#python-startup-configuration).
+This controls Python user-site loading only and does not
+change the hypervisor requirement or make this sample supported on the default
+Foundry runtime.
+
 ## Interacting with the agent
 
 Send a POST request to the server with a JSON body containing an `"input"`
diff --git a/python/samples/04-hosting/container/hyperlight_codeact/agent.manifest.yaml b/python/samples/04-hosting/container/hyperlight_codeact/agent.manifest.yaml
index 623c663291f..f04d901ed3f 100644
--- a/python/samples/04-hosting/container/hyperlight_codeact/agent.manifest.yaml
+++ b/python/samples/04-hosting/container/hyperlight_codeact/agent.manifest.yaml
@@ -16,6 +16,8 @@ template:
     - protocol: responses
       version: 1.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/container/hyperlight_codeact/agent.yaml b/python/samples/04-hosting/container/hyperlight_codeact/agent.yaml
index 3355fb51abf..abf3faef905 100644
--- a/python/samples/04-hosting/container/hyperlight_codeact/agent.yaml
+++ b/python/samples/04-hosting/container/hyperlight_codeact/agent.yaml
@@ -19,5 +19,7 @@ resources:
     cpu: "1"
     memory: 2Gi
 environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: gpt-4.1-mini
diff --git a/python/samples/04-hosting/foundry-hosted-agents/README.md b/python/samples/04-hosting/foundry-hosted-agents/README.md
index 1c91b59bfea..f2721e7c83e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/README.md
+++ b/python/samples/04-hosting/foundry-hosted-agents/README.md
@@ -5,6 +5,30 @@ This directory contains samples that demonstrate how to use hosted [Agent Framew
 > [IMPORTANT] Migrating from Protocol version 1.0.0 to 2.0.0: Foundry Hosting Agents service has been updated to use Protocol version 2.0.0. If your application is using Protocol version 1.0.0, please upgrade to Protocol version 2.0.0 in your `agent.manifest.yaml` or `agent.yaml` and upgrade to the latest `agent-framework-foundry-hosting` package. `agent-framework-foundry-hosting==1.0.0a260625` is the last version that supports Protocol version 1.0.0.
 >
 > The `agent-framework-foundry-hosting` Python API surface is intended to remain stable, but protocol 1.0.0 and 2.0.0 are incompatible.
+
+## Python startup configuration
+
+The deployment YAML files in these samples explicitly configure
+`PYTHONNOUSERSITE` with the string value `"1"` before the remote Python
+interpreter starts. Each Python Dockerfile also sets `ENV PYTHONNOUSERSITE=1`
+so directly running an image without its YAML keeps the same startup setting.
+The Telegram direct-code sample sets it in `azure.yaml` instead.
+
+This setting is configured by the customer in the sample deployment, not
+automatically injected by Foundry or Agent Framework. It disables Python
+user-site loading, not all code execution, and does not configure other
+language runtimes. Existing deployments need a newly deployed agent version
+to pick up the setting; editing a local YAML file does not update a running
+version.
+
+Install dependencies in a virtual environment or the container image's
+system site-packages, not with `pip install --user`. The samples' `pip` and
+`uv` installation paths do not require user-site packages.
+
+Keep this setting in the deployment environment or Python Dockerfile, rather
+than adding it to individual run commands. Setting `os.environ` or loading a
+`.env` file from application code is too late for Python startup.
+
 ## Samples
 
 ### Responses API
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/README.md b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/README.md
index 37283c6edce..578b6c12a31 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/README.md
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/README.md
@@ -107,6 +107,9 @@ native workflow API is published. From `python/`, run:
 uv run --no-sync python samples/04-hosting/foundry-hosted-agents/invocations/basic/workflow.py
 ```
 
+For deployment environment settings, see the
+[Python startup configuration](../../README.md#python-startup-configuration).
+
 After that release, the script's PEP 723 metadata also supports
 `uv run --script --prerelease=allow workflow.py`. Do not change a
 `pyproject.toml` to install sample-only imports. This entrypoint does not read
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.manifest.yaml
index ac71182ab62..643cac9bcbe 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: invocations
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.yaml
index b42a6df045a..db1f3d8fcf7 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/basic/agent.yaml
@@ -7,3 +7,6 @@ protocols:
 resources:
   cpu: "0.25"
   memory: "0.5Gi"
+environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.manifest.yaml
index ac71182ab62..643cac9bcbe 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: invocations
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.yaml
index b42a6df045a..db1f3d8fcf7 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/break_glass/agent.yaml
@@ -7,3 +7,6 @@ protocols:
 resources:
   cpu: "0.25"
   memory: "0.5Gi"
+environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/azure.yaml b/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/azure.yaml
index d5989239be9..e572952c896 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/azure.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/azure.yaml
@@ -20,6 +20,8 @@ services:
       Telegram bot routed through API Management to an Agent Framework agent
       using the Foundry Invocations 2.0 protocol.
     environmentVariables:
+      - name: PYTHONNOUSERSITE
+        value: "1"
       - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
         value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
       - name: AZURE_COSMOS_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/tests/test_infrastructure.py b/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/tests/test_infrastructure.py
index ba3153605f8..bc18af66514 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/tests/test_infrastructure.py
+++ b/python/samples/04-hosting/foundry-hosted-agents/invocations/telegram/tests/test_infrastructure.py
@@ -22,6 +22,7 @@ def test_direct_code_invocations_2_configuration() -> None:
         "runtime": "python_3_13",
     }
     assert service["protocols"] == [{"protocol": "invocations", "version": "2.0.0"}]
+    assert {"name": "PYTHONNOUSERSITE", "value": "1"} in service["environmentVariables"]
 
 
 def test_dependencies_use_sample_local_pyproject() -> None:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/Dockerfile
index 0cc939d9b3a..75e65e952d4 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.manifest.yaml
index 5167dfcaef9..d8c0cd58afc 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.manifest.yaml
@@ -18,6 +18,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: AZURE_SEARCH_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.yaml
index 7ffb60057c5..3b27a586335 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/azure_search_rag/agent.yaml
@@ -8,6 +8,8 @@ resources:
   cpu: "0.25"
   memory: "0.5Gi"
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: AZURE_SEARCH_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/README.md b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/README.md
index d9b46fcd7f0..6ba33391f7d 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/README.md
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/README.md
@@ -23,6 +23,8 @@ downstream service ID.
 
 Run one entry point at a time. The deployment manifest targets `main.py`; select another script to deploy a different
 mode. Set `FOUNDRY_PROJECT_ENDPOINT` and `FOUNDRY_MODEL` in `.env`, then run `python main.py`.
+For deployment environment configuration, see the
+[Python startup configuration](../../README.md#python-startup-configuration).
 Follow the [parent hosting guide](../../README.md) for local and deployed setup.
 
 ## Outer response storage and background
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.manifest.yaml
index 9547802be6a..ea63bcc064f 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.yaml
index 9408da5eb40..cfdcee9aed6 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/basic/agent.yaml
@@ -8,5 +8,7 @@ resources:
   cpu: "0.25"
   memory: "0.5Gi"
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/Dockerfile
index 0cc939d9b3a..75e65e952d4 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.manifest.yaml
index a045ba5333e..77239958fae 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: AZURE_COSMOS_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.yaml
index 4f8a99e5d34..84246f6ed1a 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/custom_storage/agent.yaml
@@ -8,6 +8,8 @@ resources:
   cpu: "0.25"
   memory: "0.5Gi"
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: AZURE_COSMOS_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/Dockerfile
index 82316e2210b..74662ab3a92 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/Dockerfile
@@ -6,6 +6,8 @@ FROM mcr.microsoft.com/dotnet/runtime:10.0 AS dotnet
 
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 # libicu is required by the .NET runtime for globalization support.
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.manifest.yaml
index 584120c871b..ff57ec0972d 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.manifest.yaml
@@ -17,6 +17,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.yaml
index 44ad3ede5b6..340cc05b933 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/declarative_customer_support/agent.yaml
@@ -8,5 +8,7 @@ resources:
   cpu: '0.25'
   memory: '0.5Gi'
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/files/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/files/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/files/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/files/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.manifest.yaml
index 01576e0e7f2..ab4f471e967 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: TOOLBOX_NAME
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.yaml
index 816e6cc15f1..b7189c871a4 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/files/agent.yaml
@@ -8,6 +8,8 @@ resources:
   cpu: "0.25"
   memory: "0.5Gi"
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: TOOLBOX_NAME
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/Dockerfile
index 0cc939d9b3a..75e65e952d4 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.manifest.yaml
index 060e96adec7..0debe4ea604 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.manifest.yaml
@@ -18,6 +18,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: MEMORY_STORE_NAME
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.yaml
index 53691375eee..80822778b66 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_memory/agent.yaml
@@ -8,6 +8,8 @@ resources:
   cpu: "0.25"
   memory: "0.5Gi"
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: MEMORY_STORE_NAME
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/Dockerfile
index 6a5bde6d263..eca43e28f91 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 RUN apt-get update && apt-get install -y git && rm -rf /var/lib/apt/lists/*
 
 WORKDIR /app
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/README.md b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/README.md
index 78393322a1f..036887e84d7 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/README.md
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/README.md
@@ -198,6 +198,9 @@ azd deploy --all
 azd ai agent run
 ```
 
+For deployment environment settings, see the
+[Python startup configuration](../../README.md#python-startup-configuration).
+
 The agent host will start on `http://localhost:8088`.
 
 #### Invoke the local agent
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.manifest.yaml
index 770bb0100ff..6fa0881dd4c 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: TOOLBOX_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.yaml
index 3711356799e..0b24c0a77dd 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox/agent.yaml
@@ -7,6 +7,8 @@ resources:
   cpu: "0.25"
   memory: 0.5Gi
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: TOOLBOX_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/Dockerfile
index 12c4791bc9f..cfa20f498d0 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 RUN apt-get update && apt-get install -y git && rm -rf /var/lib/apt/lists/*
 
 WORKDIR /app
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.manifest.yaml
index 148e7ad11fa..83ce4709c9b 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.manifest.yaml
@@ -27,6 +27,8 @@ template:
     cpu: "0.25"
     memory: 0.5Gi
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: TOOLBOX_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.yaml
index 75d676ed187..76736ecf0ea 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/foundry_toolbox_mcp_skills/agent.yaml
@@ -8,6 +8,8 @@ resources:
   cpu: "0.25"
   memory: 0.5Gi
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: TOOLBOX_ENDPOINT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.manifest.yaml
index 70eae4a779f..c797d505173 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: GITHUB_PAT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.yaml
index 5f9fb3d6add..3fc91eb2f7d 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/mcp/agent.yaml
@@ -7,6 +7,8 @@ resources:
   cpu: "0.25"
   memory: 0.5Gi
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: GITHUB_PAT
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/Dockerfile
index 514bc9a0d02..bd1e3b62837 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 # Bring in the `uv` binary from a pinned Astral image. Update this tag intentionally;
 # `latest` would make rebuilds non-deterministic.
 COPY --from=ghcr.io/astral-sh/uv:0.11.6 /uv /uvx /usr/local/bin/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/README.md b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/README.md
index 1d5751c7d6a..d1e6a2f0ebf 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/README.md
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/README.md
@@ -77,6 +77,9 @@ the dependencies declared in the script:
 uv run --script --prerelease=allow main.py
 ```
 
+For deployment environment settings, see the
+[Python startup configuration](../../README.md#python-startup-configuration).
+
 Additional sample imports belong in inline script metadata, not a workspace,
 package or sample `pyproject.toml`. Before the coordinated hosting beta is
 published, use the current workspace's installed packages
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.manifest.yaml
index cf678721b52..4918a2801f0 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.manifest.yaml
@@ -16,6 +16,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: ENABLE_INSTRUMENTATION
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.yaml
index 041f5a5745a..bf07346085c 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/monty_codeact/agent.yaml
@@ -7,6 +7,8 @@ resources:
   cpu: "0.25"
   memory: 0.5Gi
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: ENABLE_INSTRUMENTATION
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/observability/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/observability/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/observability/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/observability/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.manifest.yaml
index 2d5f20c3d86..e5f14b948b4 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
     - name: ENABLE_SENSITIVE_DATA
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.yaml
index 6ce2a78704a..edda4f822c9 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/observability/agent.yaml
@@ -8,6 +8,8 @@ resources:
   cpu: "0.25"
   memory: "0.5Gi"
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
   - name: ENABLE_SENSITIVE_DATA
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.manifest.yaml
index 7502e04fc2f..a29d2795fe3 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.manifest.yaml
@@ -16,3 +16,6 @@ template:
   protocols:
     - protocol: responses
       version: 2.0.0
+  environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.yaml
index 09728900fe2..685a4cce3c0 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/resilient_long_running_workflow/agent.yaml
@@ -7,3 +7,6 @@ protocols:
 resources:
   cpu: "0.25"
   memory: "0.5Gi"
+environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/Dockerfile
index 0cc939d9b3a..75e65e952d4 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.manifest.yaml
index d9a59b8b978..17e2dff3bb1 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.manifest.yaml
@@ -17,6 +17,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.yaml
index eb5b5340403..da863470a53 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/steerable_long_running_agent/agent.yaml
@@ -8,5 +8,7 @@ resources:
   cpu: "0.25"
   memory: "0.5Gi"
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/tools/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/tools/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/tools/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/tools/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.manifest.yaml
index 42840f80d34..f3f05109abf 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.yaml
index 2a27cd4f002..4039a89d058 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/tools/agent.yaml
@@ -7,5 +7,7 @@ resources:
   cpu: "0.25"
   memory: 0.5Gi
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/Dockerfile b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/Dockerfile
index eaffb94f198..e0c93a0ab5e 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/Dockerfile
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/Dockerfile
@@ -1,5 +1,7 @@
 FROM python:3.12-slim
 
+ENV PYTHONNOUSERSITE=1
+
 WORKDIR /app
 
 COPY . user_agent/
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/README.md b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/README.md
index 096980b8f58..cf895801b44 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/README.md
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/README.md
@@ -31,6 +31,9 @@ uv run --no-sync python main.py
 uv run --no-sync python approval.py
 ```
 
+For deployment environment settings, see the
+[Python startup configuration](../../README.md#python-startup-configuration).
+
 Example typed request:
 
 ```bash
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.manifest.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.manifest.yaml
index 6305ab4d792..028c8a97e39 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.manifest.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.manifest.yaml
@@ -15,6 +15,8 @@ template:
     - protocol: responses
       version: 2.0.0
   environment_variables:
+    - name: PYTHONNOUSERSITE
+      value: "1"
     - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
       value: "{{AZURE_AI_MODEL_DEPLOYMENT_NAME}}"
 resources:
diff --git a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.yaml b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.yaml
index db73258994b..941b65870bc 100644
--- a/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.yaml
+++ b/python/samples/04-hosting/foundry-hosted-agents/responses/workflows/agent.yaml
@@ -7,5 +7,7 @@ resources:
   cpu: "0.25"
   memory: 0.5Gi
 environment_variables:
+  - name: PYTHONNOUSERSITE
+    value: "1"
   - name: AZURE_AI_MODEL_DEPLOYMENT_NAME
     value: ${AZURE_AI_MODEL_DEPLOYMENT_NAME}
diff --git a/skills/agent-framework-builder-python/references/hosting-and-deployment.md b/skills/agent-framework-builder-python/references/hosting-and-deployment.md
index 480c09fc374..8b0dc4afb1e 100644
--- a/skills/agent-framework-builder-python/references/hosting-and-deployment.md
+++ b/skills/agent-framework-builder-python/references/hosting-and-deployment.md
@@ -35,6 +35,16 @@ Verify the entry point imports, required packages and external files are include
 and storage ownership are documented, request-owned resources are cleaned up, and no local credentials or caches enter
 the deployment package.
 
+For Python Foundry hosted agents, configure `PYTHONNOUSERSITE=1` in the
+deployment environment before Python starts, and in the Dockerfile for images
+also launched without that deployment definition. Setting it inside application
+code or a `.env` file loaded by Python is too late for startup. Install dependencies
+in a virtual environment or image system site-packages, not with `pip install --user`.
+This customer-configured setting disables Python user-site loading, not all
+code execution or other language runtimes. Redeploy a new agent version to
+apply it to existing deployments. See the
+[maintained sample startup guidance](https://github.com/microsoft/agent-framework/tree/main/python/samples/04-hosting/foundry-hosted-agents#python-startup-configuration).
+
 ## Deploy to Microsoft Foundry
 
 Foundry deployment commands, manifests, prerequisites, and injected configuration change independently from Agent