Software:
- firewall, no inbound and do outbound restrictions
- use immutable OS
- full disk encryption (keep in mind that in many setups you will need to be beside the computer after restart)
Hardware:
- put it in the trusted datacenter (home stuff is not safe from teenagers and people that need computer's electrical socket for a vacuum cleaner)
NixOS is a Linux distro that does a lot of things differently (for the greater good), and gaming is heavily Windows thing, which is hard to do even on conventional Linux distros (its getting better tho). That said as for your points:
1a. One of the things that would help you, is
programs.nix-ld.enable = true;
(for more info check https://github.com/Mic92/nix-ld , but its integrated in NixOS already)1b. UE5 pull request has some things that might help (eg: you could just try running it with steam-run): https://github.com/NixOS/nixpkgs/issues/124963
Depends how you are building them, I am not a gaming developer nor tried to build a game without packaging it with Nix. But if you manage to run the UE5 I guess the procedure would be the same as long as you have all of the dependencies available for UE5
I am using qemu/KVM on NixOS to run games on with quite a good performance, so that should not be a problem