diff --git a/Modules/Bridge/NumPy/CMakeLists.txt b/Modules/Bridge/NumPy/CMakeLists.txt
index 8807e4b6954..8f734fb8c67 100644
--- a/Modules/Bridge/NumPy/CMakeLists.txt
+++ b/Modules/Bridge/NumPy/CMakeLists.txt
@@ -1,7 +1,9 @@
 cmake_minimum_required(VERSION 3.16.3)
 project(ITKBridgeNumPy)
 
-set(ITKBridgeNumPy_SYSTEM_INCLUDE_DIRS "${Python3_INCLUDE_DIRS}")
+# Don't set SYSTEM_INCLUDE_DIRS for Python - handle includes separately
+# to avoid CMake errors about source-prefixed paths in INTERFACE properties
+set(ITKBridgeNumPy_SYSTEM_INCLUDE_DIRS "")
 
 if(NOT ITK_SOURCE_DIR)
   find_package(ITK REQUIRED)
@@ -10,3 +12,13 @@ if(NOT ITK_SOURCE_DIR)
 else()
   itk_module_impl()
 endif()
+
+# Add Python includes using BUILD_INTERFACE generator expression
+# This ensures they're only used during build, not in exports
+if(Python3_INCLUDE_DIRS AND TARGET ITKBridgeNumPyModule)
+  target_include_directories(ITKBridgeNumPyModule
+    SYSTEM
+    INTERFACE
+      $<BUILD_INTERFACE:${Python3_INCLUDE_DIRS}>
+  )
+endif()