Indeed, but it's somewhat of a hassle. Having everything integrated on the board, or in the same case, is nicer.

YIL a Pi 4B can run from a directly connected USB/NVME SSD. I've been using USB/SATA SSDs and all I have tried require a powered hub. Do note that I don't just just boot it up and proclaim "It boots - ship it"[1] I thrash it with various disk benchmarks and stress tests to be absolutely certain the SSD does not disconnect due to insufficient power.

[1] I suppose this is the H/W equivalent of the S/W engineer's proclamation "It compiles - ship it!" And I guess this dates me since S/W is pushed rather than shipped these days.