nix is a "native" packaging format. Apps are compiled for your host OS and run in that environment with no restrictions, for better or worse.

Flatpaks are containers. They provide a virtual OS to the application such as the file system, and accessing host OS features is done through "portals" which just means you can give/revoke the ability of the app to access your host OS resources such as networking, file access etc.

Flatpaks are therefore much safer in theory. But Nix packages are lower overhead, and can interact like any built-in software binary that you'd have when you spin up a fresh install of, say, debian.

Nix packages are harder to use IMO thanks to their poor documentation and lack of GUI package manager support (not that it's impossible, just that it's been a niche system for most of its life) and since most people are accustomed to flatpaks and their permissions system (and the fact it comes preinstalled on most distros) so flatpak is still pretty ubiquitous, even for NIxOS users