I'm gonna assume there will be a time skip from the end of TR:S 2 if Cade's the MC
Gonna be funny to watch the forums if this is ever announced. The incest crowd is gonna come in hot because he's got like a dozen sisters, and leave very disappointed. I'd be fine with another Garret story though, plenty of content left there. People are gonna find out about the Gaia-class world at some point and cause problems.
I don't recall if there were any plot points left open at the end of TRS2 or not.
You'd have to find a good reason to separate Cade and his father's story a bit to tell a good Cade story, maybe on a ship Mass Effect style.
Edit: Just came across a couple plot points that weren't fully explored while doing another playthrough. It's briefly brought up that humans might not be the original sapient species on Earth. There is also the mystery behind the race on Caeria being there one day and then gone the next.