I know that it’s not possible to boot hassio from usb. So what I would like to do is boot my raspberry pi 3b+ from an sd card, but run home assistant from my usb drive. Is that possible?
You could install Raspbian Stretch onto a usb drive and once that is up and running enable SSH via raspi-config then install a Generic version of hassio installing any necessary requirements. Setup WiFi from the desktop if you intend to use that and not Ethernet.
I have this running on a spare 3B not 3B+ on an SSD. 3B+ has usb boot natively, as far as I can tell, so this should be possible.