The SQLite limitations might also be solvable by sharding the databases (so each sees 1/N of the write volume), tiering them (so tiles that are written most recently are in file A, then file B, then file C), or a combination of these approaches.
I'm assuming the requirement is not really to build a single .mbtiles file, but to have some way for a process to serve the correct tile when given a z/x/y tuple.
I'm assuming the requirement is not really to build a single .mbtiles file, but to have some way for a process to serve the correct tile when given a z/x/y tuple.