Did you ever attempt to use PyPy? Flask works with it, and in my experience the handful of times I've needed Python to be more performant, PyPy got me there easily.

My use-case was I was doing a heavy part of an ETL pipeline out of MySQL and it was taking an unreasonable amount of time. PyPy was a roughly ~8x speedup, which ended up being faster than doing direct manipulation with MySQL via the cli (!!!).