I have been running Hassio without any issues on a USB SSD on a 4B for a few months now.
My understanding is that the 4B currently can only boot from the MircoSD.
To setup, I followed this: https://jamesachambers.com/raspberry-pi-4-usb-boot-config-guide-for-ssd-flash-drives/ as mentioned above by kanga_who.
Basically, it keeps the boot partition on the MicroSD card, but uses the SSD drive for the other partitions. (You burn Hassio on both the MicroSD and the SSD, then make the MicroSD point to the SSD.)
For me, this means being able to can keep Hassio as the operating system. I don’t think there are any particular advantages in using one operating system or another. For me, though, the really big advantage was having the supervisor (putting updates and other OS-level operations into the HA UI). Also, being as close to default as I could, means I have less maintenance and fiddling to do (not that that’s bad, it’s just not for me).
Going to an SD drive speeds things up amazingly. Just do it, it is worth it.
On a negative side, I had a 3B+ which booted directly to the SD drive (with no MicroSD in the slot), and it seemed a lot faster than the above at booting. Of course, the 4B with the SD drive connected via USB 3 will be faster during normal running, but really, it doesn’t seem that much faster. After all, how much computing power is needed on a deployed system?
I wonder about the worth of upgrading to a 4B.
The 4B is more power hungry, meaning it costs more to run every minute of every day or every year. But it’s faster, which I can notice as Node Red seems smoother. But does the extra speed for the occasional update justify the extra cost all round?
This is the case on my 4B:
I like that it’s a heatsink - and that it doesn’t have a fan (why spend energy to remove wasted energy?). (If you get one, the thermal conductive pads you get break easily, so take care!) Still, it’s very warm to the touch.