I had an idea recently to try out Fedora silverblue with Guix on top.
Silverblue gives you an immutable root filesystem, which is great for building a reliable and reproducible system, but it makes installing software more complicated. Containers are the main solution, and stuff like flatpaks and toolbox. That (mostly) works, but it’s a bit heavy handed and not without annoyances.
But with guix, your packages live in the guix store, and don’t touch your os packages. So that seems like a good way to manage software on top of an immutable OS.
Unfortunately when I went to try it out, I learned that the only way to change the default location of the guix store (since /gnu/store won’t work in silverblue, and Guix isn’t available as a package for fedora) is to build it from source... and then I ran into some build issues when trying to do that and gave up.
...So maybe someone less lazy than I will pull it off and report back whether it’s actually a good idea or not!