It really depends on the languages!
There's no trouble combining C and Assembly; ultimately, C is compiled down to Assembly, at which point any Assembly code you wrote outright is just inserted in. Then, the whole thing is assembled down to binary on that particular platform.
However, you can run into varying degrees of performance issues when mixing other languages. It has to be taken on a case-by-case basis.
Bravo on making a game for Sega Genesis! Keep us posted on dev.to how that goes.
I highly recommend picking up "Game Engine Architecture" by Jason Gregory. It addresses many of the issues you're facing, and hundreds more besides, from a C and C++ perspective. He even talks about console development.
We're a place where coders share, stay up-to-date and grow their careers.
We strive for transparency and don't collect excess data.