I'm gearing up to run a 5E campaign in a sci-fi setting. I don't have many notes to share at the moment, but I can report back when I do. I've been borrowing heavily from "Stars Without Number," "Numenara," and "Starfinder" for ideas.
Space opera sci-fi. Not psuedo-sci fi fantasy like Starfinder or what not with D&D monsters and magic (if there's going to be any powers, make it psionics and not ubiquitous), just good sci fi.
I'd love to see Shadowrun with the D&D 5e rules. It would be an instant buy for me.
The best game of SR I was ever in was run using M:tA (oWoD Storyteller), so, IDK, a very different dynamic from the native system may not be such a bad thing...Imo that won't work very well.
D&D is much too inflexible to handle the full spectrum of SR gameplay and the combat system would create a completely different dynamic than what SR goes for.
Base D&D rules don't handle guns very well though.
They don't handle guns very well if they're bolted on top of existing medieval weapons, and treated as something different and special. But if you just take the stats of standard slings and crossbows and longbows, and change the names to phasers / blasters / whatever, then D&D handles guns just fine.