Most of the issues come from the lack of enthusiasm for moving the Nix store somewhere else than /nix. Even with read-only root, macOS has some designated locations where you can write. E.g. Homebrew uses /opt/homebrew, which is fine because /opt is writable.

I understand the reasoning of avoiding this on Intel Macs, since there there are years of cached derivations which would become useless without hacks. However, Apple Silicon Macs are a clean slate and the transition would've been a good occasion to move the store to /opt/nix.

(I did suggest this in some places, but there didn't seem to be much interest in switching over, unless I missed something.)

By the way, this isn't only an issue with macOS. Nix also doesn't work on Fedora Silverblue because it uses read-only root and the Nix store path violates FHS.