Thanks for interesting Post. Why not just believe in Cython (with released GIL) for that 10% of code that uses 90% of Execution Time. ;) Although pypy is really amazing but no idea when it will be ready for Production. One of my friend was working in interesting Project just like Cython but seems now it is under no development.(https://github.com/pradyunsg/Py2C) I tried many things in my nights to learn and live more with Multiprocessing Python using All CPU cores but now I came in the face that may be Pyjulia (https://github.com/JuliaPy/pyjulia) or Julia could be the real answer.(https://julialang.org/) BTW have you tried Py-Parallel?