I'm kind of surprised to hear that was a concern because my perception is that PyO3 is more analogous to wrapping native C code in Python libraries (which is pretty well established since long before either Rust or WASM), and Pyodide seems more like something for use in browsers rather on the server-side. When I looked into this earlier this year, trying to run Python via WASM on the server side with Pyodide had a bunch of hoops I needed to jump through, and it ended up being a lot simpler to use a build of Python from one of the core Python contributors that directly targeted WASM.

Yes, Pyodide is almost entirely used in web browsers. I want to be able to run existing code that uses libraries like Pyodide-core in a browser.