When I was packaging Flatpaks, the greatest downside is

No built in package manager

There is a repo with shared dependencies, but it is very few. So needs to package all the dependencies... So, I personally am not interested in packaging for flatpak other than in very rare occasions... Nix and Guix are definitely better solutions (except the isolation aspect, which is not a feature, you need to do it manually), and one can use at many distros; Nix even on MacOS!

Some of them will detect if using virtualization. For example http://safeexambrowser.org/ by ETH Zurich

Ironically enough, it is free software https://github.com/SafeExamBrowser