I've run my mini2018 from external for about an year.
One thing to remember is that if your homedir is not on boot volume, you'll get zero support from apple.
So, because I had migration problems with appleMail, I don't use the (too small) internal ssd at all.
Another case, where the support stops, is if you are running something else than the latest OS. I found out this, because I'm running Mojave, because I own CS6 and don't want to pay more to adobe.
If anybody knows if this has changed with Catalina:
You can only repair permissions if homedir is in bootdrive?
More about these:
Here's the problem: Home Folder in ext disk "not supported" by Apple diskutil resetUserPermissions / `id -u` Long story short: I tried to avoid apple tax by buing mini with small int ssd. Seems to be that at least for 10.14., You have to have your home folder in startup drive, otherwise you...
forums.macrumors.com
I thought that like any *nix machine, my new mac mini would work just fine, when I ordered it with small soldered ssd, which would contain System and Applications and have everything else in external drives. Since you can use cheap, but fast usb3.1g2 ssd (10Gbit/s) or even faster tb3-ssd...
forums.macrumors.com
Can anybody tell what those switches mean? Anybody researched this undocumented switch further?
forums.macrumors.com
Maybe in June, if I have the energy, I'll start tinkering with Catalina and unix-UUID's to see, if I could use the internal ssd as boot drive and homedirs in external. I already have an unused ssd for that and will order another.
I wish there would be reasonably priced tb-usb3.1g2 hub for sale. 4 usb-cp orts with 10G and tb3 for connecting to mini.