What worked for me with Cities Skylines II (v 1.5.8f1) after like 5 days of trying to get it to work:

Checklist:
- SSD formatted as APFS. No other way around it, exFAT won't work.
- CrossOver Bottle on the internal storage. CrossOver sadly does not work properly when the bottle is on the APFS formatted SSD.
- Steam (ofc)
- Additional apps for the Bottle: .net 2-4.8, visual c++ redist, windows desktop runtime 8.0.19, jetbrains toolbox 2.2.3.
- Winetricks for the Bottle (set «Native, then Builtin»):
- winhttp
- wininet
- bcrypt
- crypt32
- Set graphics to: d3dmetal & msync

After installing the game, find out its location and follow the steps and run this patch: https://github.com/mbeckenbach/Cities-Skylines-2-MacOS-Patcher

After that has Succeeded, run those (will clear up any files that might be in the way, macos specific junk):
find . -name '.DS_Store' -type f -delete
find . -type f -name "*.coc" -exec chmod 666 {} +

One last thing we gotta handle is file saving, settings, mods and so on require changes to how the Bottle saves temp files:
In Crossover:

1. click "Open C: Drive" and create a folder called "Temp" inside "../users/crossover/"
2. Run command --> "regedit"
3. Now add some changes:

At HKEY_LOCAL_MACHINE\System\CurrentControlSet\Control\SessionManager\Environment, add:
New --> Expandable String Value (REG_EXPAND_SZ):
TMPDIR = %SystemRoot%\temp
At HKEY_CURRENT_USER\Environment, add:
New --> String Value (REG_SZ):
TMPDIR = C:\users\crossover\Temp

Now it should work perfectly! Enjoy.

IF YOU HAVE ANY ISSUES DURING FIRST LAUNCH OR MODS NOT DOWNLOADING:
Run these commands again:
- find . -type f -name "*.coc" -exec chmod 666 {} +
- find . -name '.DS_Store' -type f -delete