In practice, I've very rarely seen a downside: I compare it to something like Vite, where it uses esbuild in development and rollup in production, because the two libraries are for different things (esbuild doesn't bundle, rollup does, etc).

In development, I compile it with Go. In production, I compile it with TinyGo. Yes, you need to be careful about imports, and it does add complexity, but the benefits of not managing two different completely different languages (JS and whatever you're compiling to WASM) far outweigh that cost.

As for Cloudflare, I don't think their service's benefits outweigh the complexity, but I've had luck in the past with the dual setup on Workers.