Yeah that does make a lot more sense now. Particularly the "“mame_boot_from_cli” option. Some systems need it disabled in order to boot." That wasn’t something I’d run into yet as both MESS systems (NGCD and CD-i) I use need that turned on.
I don’t know if this helps, but barring any other solution, maybe?
I know at one point I needed vastly different configurations, and I honestly just duplicated my RetroArch install to another folder named “RetroArch_Alt” and made the few changes I needed there - then set a matching module in RocketLauncher to boot to my 2nd install for the system that needed said changes.
I don’t know if you even use a frontend like that, but maybe something along those lines could be a janky work-around. Hopefully there’s a more elegant solution though. That’s a pretty hard roadblock from the sound of it right now.