This is how I run mine - SD for boot, USB SSD for root.
You can run NVMe on a Pi4, sort of... if you replace the USB3 controller with a bridge PCB that routes PCIe out the USB ports properly for some other adapters. I don't recall if they got it working reliably or not. And then if you use the CM4, you can certainly have reliable NVMe.
But I'm just not sure it really matters. USB3 SSDs, UAS or not (I've run into UAS issues and while you can tell the difference in a benchmark between having it and not, I can't tell the difference in end use) are more than fast enough for daily use.
I've done a writeup of making a Pi4 desktop here: https://www.sevarg.net/2019/12/14/building-raspberry-pi-4-de...
The only real change is that the kernel now has zswap provided as a module, so you don't need to build a kernel unless you just think building a kernel on a Pi is cool (which it indeed is).
It's not fast, but it's more than adequate for light desktop use. If you want more guts behind it, the ODroid N2+ is about twice as fast, for not an awful lot more money.