diff --git a/.changeset/blue-waves-travel.md b/.changeset/blue-waves-travel.md
new file mode 100644
index 00000000000..9f7821250cb
--- /dev/null
+++ b/.changeset/blue-waves-travel.md
@@ -0,0 +1,5 @@
+---
+'@aws-amplify/ai-constructs': minor
+---
+
+add support for bedrock system cross-region inference profiles
diff --git a/.eslint_dictionary.json b/.eslint_dictionary.json
index 73bc88ff5ff..0bcb1afc224 100644
--- a/.eslint_dictionary.json
+++ b/.eslint_dictionary.json
@@ -8,6 +8,7 @@
   "ampx",
   "anonymize",
   "anthropic",
+  "apac",
   "apns",
   "apollo",
   "appleid",
diff --git a/packages/ai-constructs/src/conversation/conversation_handler_construct.test.ts b/packages/ai-constructs/src/conversation/conversation_handler_construct.test.ts
index d274e169f0f..09e41d07170 100644
--- a/packages/ai-constructs/src/conversation/conversation_handler_construct.test.ts
+++ b/packages/ai-constructs/src/conversation/conversation_handler_construct.test.ts
@@ -414,4 +414,145 @@ void describe('Conversation Handler Function construct', () => {
       });
     });
   });
+
+  void describe('cross-region models', () => {
+    void it('creates handler with access to eu cross-region models and inference profiles', () => {
+      const app = new App();
+      const stack = new Stack(app, 'TestStack', {
+        env: { region: 'eu-west-1' },
+      });
+      new ConversationHandlerFunction(stack, 'conversationHandler', {
+        models: [
+          {
+            modelId: 'eu.anthropic.claude-3-5-sonnet-20240620-v1:0',
+          },
+        ],
+      });
+
+      const template = Template.fromStack(stack);
+      template.hasResourceProperties('AWS::IAM::Policy', {
+        PolicyDocument: {
+          Statement: [
+            {
+              Action: [
+                'bedrock:InvokeModel',
+                'bedrock:InvokeModelWithResponseStream',
+              ],
+              Effect: 'Allow',
+              Resource: [
+                {
+                  'Fn::Join': [
+                    '',
+                    [
+                      'arn:aws:bedrock:eu-west-1:',
+                      {
+                        Ref: 'AWS::AccountId',
+                      },
+                      ':inference-profile/eu.anthropic.claude-3-5-sonnet-20240620-v1:0',
+                    ],
+                  ],
+                },
+                'arn:aws:bedrock:eu-west-1::foundation-model/anthropic.claude-3-5-sonnet-20240620-v1:0',
+                'arn:aws:bedrock:eu-west-3::foundation-model/anthropic.claude-3-5-sonnet-20240620-v1:0',
+                'arn:aws:bedrock:eu-central-1::foundation-model/anthropic.claude-3-5-sonnet-20240620-v1:0',
+              ],
+            },
+          ],
+        },
+      });
+    });
+
+    void it('creates handler with access to us cross-region models and inference profiles', () => {
+      const app = new App();
+      const stack = new Stack(app, 'TestStack', {
+        env: { region: 'us-east-1' },
+      });
+      new ConversationHandlerFunction(stack, 'conversationHandler', {
+        models: [
+          {
+            modelId: 'us.anthropic.claude-3-7-sonnet-20250219-v1:0',
+          },
+        ],
+      });
+
+      const template = Template.fromStack(stack);
+      template.hasResourceProperties('AWS::IAM::Policy', {
+        PolicyDocument: {
+          Statement: [
+            {
+              Action: [
+                'bedrock:InvokeModel',
+                'bedrock:InvokeModelWithResponseStream',
+              ],
+              Effect: 'Allow',
+              Resource: [
+                {
+                  'Fn::Join': [
+                    '',
+                    [
+                      'arn:aws:bedrock:us-east-1:',
+                      {
+                        Ref: 'AWS::AccountId',
+                      },
+                      ':inference-profile/us.anthropic.claude-3-7-sonnet-20250219-v1:0',
+                    ],
+                  ],
+                },
+                'arn:aws:bedrock:us-east-1::foundation-model/anthropic.claude-3-7-sonnet-20250219-v1:0',
+                'arn:aws:bedrock:us-east-2::foundation-model/anthropic.claude-3-7-sonnet-20250219-v1:0',
+                'arn:aws:bedrock:us-west-2::foundation-model/anthropic.claude-3-7-sonnet-20250219-v1:0',
+              ],
+            },
+          ],
+        },
+      });
+    });
+
+    void it('creates handler with access to apac cross-region models and inference profiles', () => {
+      const app = new App();
+      const stack = new Stack(app, 'TestStack', {
+        env: { region: 'ap-northeast-1' },
+      });
+      new ConversationHandlerFunction(stack, 'conversationHandler', {
+        models: [
+          {
+            modelId: 'apac.anthropic.claude-3-haiku-20240307-v1:0',
+          },
+        ],
+      });
+
+      const template = Template.fromStack(stack);
+      template.hasResourceProperties('AWS::IAM::Policy', {
+        PolicyDocument: {
+          Statement: [
+            {
+              Action: [
+                'bedrock:InvokeModel',
+                'bedrock:InvokeModelWithResponseStream',
+              ],
+              Effect: 'Allow',
+              Resource: [
+                {
+                  'Fn::Join': [
+                    '',
+                    [
+                      'arn:aws:bedrock:ap-northeast-1:',
+                      {
+                        Ref: 'AWS::AccountId',
+                      },
+                      ':inference-profile/apac.anthropic.claude-3-haiku-20240307-v1:0',
+                    ],
+                  ],
+                },
+                'arn:aws:bedrock:ap-northeast-1::foundation-model/anthropic.claude-3-haiku-20240307-v1:0',
+                'arn:aws:bedrock:ap-northeast-2::foundation-model/anthropic.claude-3-haiku-20240307-v1:0',
+                'arn:aws:bedrock:ap-southeast-1::foundation-model/anthropic.claude-3-haiku-20240307-v1:0',
+                'arn:aws:bedrock:ap-southeast-2::foundation-model/anthropic.claude-3-haiku-20240307-v1:0',
+              ],
+            },
+          ],
+        },
+      });
+    });
+  });
 });
diff --git a/packages/ai-constructs/src/conversation/conversation_handler_construct.ts b/packages/ai-constructs/src/conversation/conversation_handler_construct.ts
index 36c19c66d35..ecaaa260d63 100644
--- a/packages/ai-constructs/src/conversation/conversation_handler_construct.ts
+++ b/packages/ai-constructs/src/conversation/conversation_handler_construct.ts
@@ -130,12 +130,7 @@ export class ConversationHandlerFunction
     );
 
     if (this.props.models && this.props.models.length > 0) {
-      const resources = this.props.models.map(
-        (model) =>
-          `arn:aws:bedrock:${
-            model.region ?? Stack.of(this).region
-          }::foundation-model/${model.modelId}`
-      );
+      const resources = this.generateIamPolicyResourceBlocks(this.props.models);
       conversationHandler.addToRolePolicy(
         new PolicyStatement({
           effect: Effect.ALLOW,
@@ -160,6 +155,53 @@ export class ConversationHandlerFunction
     this.storeOutput(this.props.outputStorageStrategy);
   }
 
+  private generateIamPolicyResourceBlocks = (
+    models: { modelId: string; region?: string }[]
+  ): string[] => {
+    const crossRegionInferenceProfileRegions: Record<string, string[]> = {
+      'eu.': ['eu-west-1', 'eu-west-3', 'eu-central-1'],
+      'us.': ['us-east-1', 'us-east-2', 'us-west-2'],
+      'apac.': [
+        'ap-northeast-1',
+        'ap-northeast-2',
+        'ap-southeast-1',
+        'ap-southeast-2',
+      ],
+    };
+    const resourceBlocks = models.map((model) => {
+      const region = model.region ?? Stack.of(this).region;
+      const modelPrefix = Object.keys(crossRegionInferenceProfileRegions).find(
+        (prefix) => model.modelId.startsWith(prefix)
+      );
+
+      if (modelPrefix) {
+        // For cross-region models, generate resource blocks for all supported regions
+        const foundationModelResourceBlocks =
+          crossRegionInferenceProfileRegions[modelPrefix].map(
+            (region) =>
+              `arn:aws:bedrock:${region}::foundation-model/${model.modelId.substring(
+                modelPrefix.length
+              )}`
+          );
+
+        // For cross-region models, also generate inference profile resource blocks
+        const inferenceProfileResourceBlock = `arn:aws:bedrock:${region}:${
+          Stack.of(this).account
+        }:inference-profile/${model.modelId}`;
+
+        return [
+          inferenceProfileResourceBlock,
+          ...foundationModelResourceBlocks,
+        ];
+      }
+
+      // For non-cross-region models, use the specified or stack region
+      return [`arn:aws:bedrock:${region}::foundation-model/${model.modelId}`];
+    });
+
+    return resourceBlocks.flat();
+  };
+
   /**
    * Append conversation handler to defined functions.
    */