I never could get an external boot drive to work on my 2016? iMac . Beyond that you could apply your question to almost any segment of console or PC gaming. External SSD's over USB3.0 deliver marked improvements. There are minor latency and overhead penalties but in practice they are not noticeable. TBH, I play TW games myself and, I couldn't really tell you that I've noticed any difference whether it was on my SATA based SSD or the 3.3GB/S WD Black NVME drive I have too.
The question you should probably be asking and researching is which enclosure is going to give you the most reliable performance. Just because a 2.5" enclosure says it's USB 3.0 does not necessarily mean that you're going to hit 450MB/s sequential and 25-30MB/S 4K read/writes.
I did find that there was some significant variations depending on what controller was used(some sacrificed large sequential for 4K which isn't what you want, some couldn't maintain performance and overheated quickly) and unfortunately the only way to really find something that won't bottleneck the drive further is to read recent reviews on amazon and buy a couple of enclosures.
it looks like they no longer make the drive I found that worked best (an inateck with a VIA controller) but they have an updated version for $9 that may be a good place to start
edit; it was a Noriesys controller but the date stamp is from 2013 (and I bought around 2016) so it's proabably no longer relevant information.