Little Snitch is basically a user-friendly general-purpose application Firewall. When a connection hasn't been whitelisted before, it pop up a dialog box allowing you to accept/reject connection to a host/domain/port permanently/temporarily.
uMatrix does not protect you against 'malicious' connections initiated by non-browser applications. Little Snitch does not provide the fine-grained URI-level filtering that uBlock/uMatrix provide.
Edit: if you have a Mac, Little Snitch is well-worth the money. It is very polished, does the job, and the developers are not greedy (I think I purchased an update once after I started using it in 2007 or 2008).
Maybe, but I haven't found anything as polished as Little Snitch. The level of control is amazingly high. I really don't use it to the full extent with profiles and the like. I set up some basic rules and let it work for awhile, then I pick and choose what to allow/disallow permanently... like a King :P
It's one of the first things I install on my Macs. Worth every penny.
Then add iptables to that list and I think you're set :-) seriously, all due respect to Little Snitch - I've heard a lot of good things about it and I'm sure it's much easier to use than the raw tools. But I doubt it's doing anything that can't be done with tcpdump/iptables.