I migrated my main personal project (a programming language written in C) to Tup recently. So far I love it, it seems to 'just work'. Some highlights:

No need to map header (or other) files to C files. Tup detects when files are read and adds them as implicit dependencies.

Environment variables (that are used) are considered build inputs, so no need to `make clean` when you need a build with debug symbols.

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Admittedly my project is quite straightforward, but I thoroughly recommend giving Tup a try.