I hope you've got it working before me posting this. I just ran into a similar problem about 2-3 days ago. I even ended up on the phone with Tech support, and truthfully -- no solid answers except Murphy (Murphy's Law) and his b*****d gremlins. Here is what I DID do and then we walked through all the settings (on the 3rd time).
I am running on a Windows 10 OS with a custom built workhorse tower. I started off with a StudioLive AR12 USB Hybrid Mixer and The Artist Edition Software to try it out. I honestly do love this software and the mixers (and I have worked with a lot of different things).
First -- I completely uninstalled Studio Live and all the Plugins, Universal Controller, then a complete disc defrag (I'm not running a solid state drive). Then reinstall the program, then the universal controller, and it would see the mixer, it recognized my inputs and MIDI, but even with the Mains bouncing on the screen -- I had no sound. (I had sound on the computer -- e.g. youtube videos, CD player, etc. -- but nothing from the program)
I actually did those steps twice with no luck. This morning, I did the rinse and repeat of this and reinstalled a third time and got on the phone with the tech. We checked all the inputs and audio (yes on regular mp3s and videos) nothing on mixer. Went in and checked the default audio settings, and then relaunched the program and it worked. We still don't know what is different -- nothing changed. Sometimes, I think the Windows updates confuse the plugins and maybe that was all it was. The tech did mention that sometimes the audio will reset to the default settings and that will mess it up.
Seriously. I'm not getting rid of this program.I still love it. I still blame Murphy and his web gremlin b*****ds.
** Update to this problem ** Thank you Luke !!** here's the fix that solved my issues. Not sure if you're using a PreSonus mixer but this did help. https://support.presonus.com/hc/en-us/articles/360029682252-Series-III-Studio-One-Playback-to-the-TAPE-IN-channel-when-in-DAW-Mode