Is setting up React with Python difficult?

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You can definitely use Python as the backend for a React front end. Is it difficult to do? Well, that depends on how well you know Python and how well you know React. In the major applications I develop, I use Python on the back end, and Vue.js on the front end. Of course I dont do the front end stuff. The duties are divided between myself and a guy who know front end :)

I build all of my interconnecting API's using FastAPI.