Easy enough to do (although it needs a new part) but perhaps not wise. I put the holes in because the original part from the Raspberry PI folks indicated this was a keepout area and had the holes drilled (I assumed, as I don’t have a board that the pins from the USB stuck down.) It may also be that running traces under the USB will affect the USB 3 signalling, but if this works for you, this part doesn’t have the holes in the USB area.
Raspberry-Pi-Pico-smd-noUSB-holes.fzpz (22.7 KB)
Peter