This is better achieved with the compiler level tooling, rather than in Make. It's pretty easy to replace `cc` with a short script that runs the pre-compiler and compares the result with a cache.

If the source code is kept tight, it doesn't yield much of a speed-up, though - precompiling hundreds of unnecessary headers can take a lot of time. Better to put some effort into moving unnecessary #includes out of header files. In fact, you can use your log of cache-hits to guide that work.

I also wish I could make certain variables/flags part of the dependencies of a file, like if I have something with a lot of #defines that I really want to rebuild any time CPPFLAGS changes

This might be worth building into the makefile interpreter. Doing it in the makefiles themselves is quite difficult to get right and very messy.