diff --git a/source/extensions/common/wasm/context.cc b/source/extensions/common/wasm/context.cc
index 8651b98ef4b32..b7e404bcffe5f 100644
--- a/source/extensions/common/wasm/context.cc
+++ b/source/extensions/common/wasm/context.cc
@@ -708,6 +708,9 @@ WasmResult Context::addHeaderMapValue(WasmHeaderMapType type, absl::string_view
   }
   const Http::LowerCaseString lower_key{std::string(key)};
   map->addCopy(lower_key, std::string(value));
+  if (type == WasmHeaderMapType::RequestHeaders) {
+    decoder_callbacks_->clearRouteCache();
+  }
   return WasmResult::Ok;
 }
 
@@ -769,6 +772,9 @@ WasmResult Context::setHeaderMapPairs(WasmHeaderMapType type, const Pairs& pairs
     const Http::LowerCaseString lower_key{std::string(p.first)};
     map->addCopy(lower_key, std::string(p.second));
   }
+  if (type == WasmHeaderMapType::RequestHeaders) {
+    decoder_callbacks_->clearRouteCache();
+  }
   return WasmResult::Ok;
 }
 
@@ -779,6 +785,9 @@ WasmResult Context::removeHeaderMapValue(WasmHeaderMapType type, absl::string_vi
   }
   const Http::LowerCaseString lower_key{std::string(key)};
   map->remove(lower_key);
+  if (type == WasmHeaderMapType::RequestHeaders) {
+    decoder_callbacks_->clearRouteCache();
+  }
   return WasmResult::Ok;
 }
 
@@ -790,6 +799,9 @@ WasmResult Context::replaceHeaderMapValue(WasmHeaderMapType type, absl::string_v
   }
   const Http::LowerCaseString lower_key{std::string(key)};
   map->setCopy(lower_key, value);
+  if (type == WasmHeaderMapType::RequestHeaders) {
+    decoder_callbacks_->clearRouteCache();
+  }
   return WasmResult::Ok;
 }
 
diff --git a/test/extensions/filters/http/wasm/test_data/headers_rust.rs b/test/extensions/filters/http/wasm/test_data/headers_rust.rs
index 6d9fc94a7a9cc..dbdaff1368780 100644
--- a/test/extensions/filters/http/wasm/test_data/headers_rust.rs
+++ b/test/extensions/filters/http/wasm/test_data/headers_rust.rs
@@ -36,6 +36,11 @@ impl HttpContext for TestStream {
         Action::Continue
     }
 
+    fn on_http_response_headers(&mut self, _: usize) -> Action {
+        self.set_http_response_header("test-status", Some("OK"));
+        Action::Continue
+    }
+
     fn on_http_response_trailers(&mut self, _: usize) -> Action {
         Action::Pause
     }
diff --git a/test/extensions/filters/http/wasm/test_data/test_cpp.cc b/test/extensions/filters/http/wasm/test_data/test_cpp.cc
index 3e009a3da8c31..f09b6198f835e 100644
--- a/test/extensions/filters/http/wasm/test_data/test_cpp.cc
+++ b/test/extensions/filters/http/wasm/test_data/test_cpp.cc
@@ -35,6 +35,7 @@ class TestContext : public Context {
 
   FilterHeadersStatus onRequestHeaders(uint32_t, bool) override;
   FilterTrailersStatus onRequestTrailers(uint32_t) override;
+  FilterHeadersStatus onResponseHeaders(uint32_t, bool) override;
   FilterTrailersStatus onResponseTrailers(uint32_t) override;
   FilterDataStatus onRequestBody(size_t body_buffer_length, bool end_of_stream) override;
   void onLog() override;
@@ -277,6 +278,15 @@ FilterTrailersStatus TestContext::onRequestTrailers(uint32_t) {
   return FilterTrailersStatus::Continue;
 }
 
+FilterHeadersStatus TestContext::onResponseHeaders(uint32_t, bool) {
+  root()->stream_context_id_ = id();
+  auto test = root()->test_;
+  if (test == "headers") {
+    CHECK_RESULT(addResponseHeader("test-status", "OK"));
+  }
+  return FilterHeadersStatus::Continue;
+}
+
 FilterTrailersStatus TestContext::onResponseTrailers(uint32_t) {
   auto value = getResponseTrailer("bogus-trailer");
   if (value && value->view() != "") {
diff --git a/test/extensions/filters/http/wasm/wasm_filter_test.cc b/test/extensions/filters/http/wasm/wasm_filter_test.cc
index fe6932f1c75c3..e7d41558991c3 100644
--- a/test/extensions/filters/http/wasm/wasm_filter_test.cc
+++ b/test/extensions/filters/http/wasm/wasm_filter_test.cc
@@ -114,6 +114,12 @@ TEST_P(WasmHttpFilterTest, HeadersOnlyRequestHeadersOnly) {
               log_(spdlog::level::debug, Eq(absl::string_view("onRequestHeaders 2 headers"))));
   EXPECT_CALL(filter(), log_(spdlog::level::info, Eq(absl::string_view("header path /"))));
   EXPECT_CALL(filter(), log_(spdlog::level::warn, Eq(absl::string_view("onDone 2"))));
+
+  // Verify that route cache is cleared when modifying HTTP request headers.
+  Http::MockStreamDecoderFilterCallbacks decoder_callbacks;
+  filter().setDecoderFilterCallbacks(decoder_callbacks);
+  EXPECT_CALL(decoder_callbacks, clearRouteCache()).Times(2);
+
   Http::TestRequestHeaderMapImpl request_headers{{":path", "/"}, {"server", "envoy"}};
   EXPECT_EQ(Http::FilterHeadersStatus::Continue, filter().decodeHeaders(request_headers, true));
   EXPECT_THAT(request_headers.get_("newheader"), Eq("newheadervalue"));
@@ -137,6 +143,12 @@ TEST_P(WasmHttpFilterTest, AllHeadersAndTrailers) {
               log_(spdlog::level::debug, Eq(absl::string_view("onRequestHeaders 2 headers"))));
   EXPECT_CALL(filter(), log_(spdlog::level::info, Eq(absl::string_view("header path /"))));
   EXPECT_CALL(filter(), log_(spdlog::level::warn, Eq(absl::string_view("onDone 2"))));
+
+  // Verify that route cache is cleared when modifying HTTP request headers.
+  Http::MockStreamDecoderFilterCallbacks decoder_callbacks;
+  filter().setDecoderFilterCallbacks(decoder_callbacks);
+  EXPECT_CALL(decoder_callbacks, clearRouteCache()).Times(2);
+
   Http::TestRequestHeaderMapImpl request_headers{{":path", "/"}, {"server", "envoy"}};
   EXPECT_EQ(Http::FilterHeadersStatus::Continue, filter().decodeHeaders(request_headers, false));
   EXPECT_THAT(request_headers.get_("newheader"), Eq("newheadervalue"));
@@ -145,8 +157,13 @@ TEST_P(WasmHttpFilterTest, AllHeadersAndTrailers) {
   EXPECT_EQ(Http::FilterTrailersStatus::Continue, filter().decodeTrailers(request_trailers));
   Http::MetadataMap request_metadata{};
   EXPECT_EQ(Http::FilterMetadataStatus::Continue, filter().decodeMetadata(request_metadata));
+
+  // Verify that route cache is NOT cleared when modifying HTTP response headers.
+  EXPECT_CALL(decoder_callbacks, clearRouteCache()).Times(0);
+
   Http::TestResponseHeaderMapImpl response_headers{};
   EXPECT_EQ(Http::FilterHeadersStatus::Continue, filter().encodeHeaders(response_headers, false));
+  EXPECT_THAT(response_headers.get_("test-status"), Eq("OK"));
   Http::TestResponseTrailerMapImpl response_trailers{};
   EXPECT_EQ(Http::FilterTrailersStatus::StopIteration, filter().encodeTrailers(response_trailers));
   Http::MetadataMap response_metadata{};