diff --git a/.changeset/vite-plugin-vitest4-resolve-external.md b/.changeset/vite-plugin-vitest4-resolve-external.md
new file mode 100644
index 0000000000..b09c19bdad
--- /dev/null
+++ b/.changeset/vite-plugin-vitest4-resolve-external.md
@@ -0,0 +1,9 @@
+---
+"@cloudflare/vite-plugin": patch
+---
+
+Allow `resolve.external` containing only Node.js built-ins in Worker environments
+
+Vitest 4 automatically sets `resolve.external` to the full list of Node.js built-in modules for non-standard Vite environments via its internal `runnerTransform` plugin. Previously, the Cloudflare Vite plugin rejected any non-empty `resolve.external` array, throwing an incompatibility error on startup when used alongside Vitest 4.
+
+The validation check now allows `resolve.external` arrays that contain only Node.js built-in module names (both bare `fs` and `node:fs` forms). The error is only thrown when `resolve.external` is `true` or contains non-built-in package names that would prevent user code from being bundled into the Worker.
diff --git a/packages/vite-plugin-cloudflare/src/__tests__/validate-worker-environment-options.spec.ts b/packages/vite-plugin-cloudflare/src/__tests__/validate-worker-environment-options.spec.ts
index 74db70c2fc..b45eccf7c1 100644
--- a/packages/vite-plugin-cloudflare/src/__tests__/validate-worker-environment-options.spec.ts
+++ b/packages/vite-plugin-cloudflare/src/__tests__/validate-worker-environment-options.spec.ts
@@ -42,6 +42,29 @@ describe("validateWorkerEnvironmentOptions", () => {
 		);
 	});
 
+	test("doesn't throw when resolve.external contains only Node.js built-ins (set by Vitest 4)", ({
+		expect,
+	}) => {
+		const resolvedPluginConfig = {
+			environmentNameToWorkerMap: new Map([["worker", { config: {} }]]),
+		} as unknown as AssetsOnlyResolvedConfig | WorkersResolvedConfig;
+		const resolvedViteConfig = {
+			environments: {
+				worker: {
+					resolve: {
+						// Vitest 4 sets resolve.external to all Node.js built-ins for
+						// non-standard environments via its runnerTransform plugin
+						external: ["assert", "buffer", "fs", "node:path", "node:fs"],
+					},
+				},
+			},
+		} as unknown as ResolvedConfig;
+
+		expect(() =>
+			validateWorkerEnvironmentOptions(resolvedPluginConfig, resolvedViteConfig)
+		).not.toThrow();
+	});
+
 	test("throws with an appropriate error message if multiple worker environments contain config violations", ({
 		expect,
 	}) => {
diff --git a/packages/vite-plugin-cloudflare/src/vite-config.ts b/packages/vite-plugin-cloudflare/src/vite-config.ts
index 32a04a5bb4..2a5ccc2171 100644
--- a/packages/vite-plugin-cloudflare/src/vite-config.ts
+++ b/packages/vite-plugin-cloudflare/src/vite-config.ts
@@ -1,10 +1,37 @@
 import assert from "node:assert";
+import { builtinModules } from "node:module";
 import type {
 	AssetsOnlyResolvedConfig,
 	WorkersResolvedConfig,
 } from "./plugin-config";
 import type * as vite from "vite";
 
+// Node.js built-in module names in both bare and `node:` prefixed forms.
+// Vitest 4 automatically adds these to `resolve.external` for non-standard
+// environments (via its `runnerTransform` plugin). They are harmless for
+// Worker environments — Workers either handle them via the node-compat layer
+// or don't use them — so validation is skipped when the array contains only
+// these entries.
+const NODE_BUILTIN_SET = new Set([
+	...builtinModules,
+	// Only add the `node:` prefix for modules that don't already have it,
+	// avoiding hypothetical `node:node:*` entries on future Node versions.
+	...builtinModules
+		.filter((m) => !m.startsWith("node:"))
+		.map((m) => `node:${m}`),
+]);
+
+function isOnlyNodeBuiltins(
+	external: vite.ResolveOptions["external"]
+): boolean {
+	if (!Array.isArray(external)) {
+		return false;
+	}
+	return external.every(
+		(entry) => typeof entry === "string" && NODE_BUILTIN_SET.has(entry)
+	);
+}
+
 interface DisallowedEnvironmentOptions {
 	resolveExternal?: vite.ResolveOptions["external"];
 }
@@ -30,7 +57,11 @@ export function validateWorkerEnvironmentOptions(
 		const { resolve } = environmentOptions;
 		const disallowedEnvironmentOptions: DisallowedEnvironmentOptions = {};
 
-		if (resolve.external === true || resolve.external.length) {
+		if (
+			(resolve.external === true ||
+				(Array.isArray(resolve.external) && resolve.external.length > 0)) &&
+			!isOnlyNodeBuiltins(resolve.external)
+		) {
 			disallowedEnvironmentOptions.resolveExternal = resolve.external;
 		}