So finally find time to do what you have suggested; I've removed the thumbnails database and, as expected, they had to be regenerated on next start. The app still freezes during that process (the impact is very, very significant, I had to wait for good 15-20 minutes to have the bottom of "Noises" generated).
More importantly, it's not only Substance Designer app that freezes, it's the entire system.
One other very important fact: the "Updating Library..." is not the only place where freezing occurs. It definitely freezes for 30-60 seconds right when the application starts, then randomly when projects are being open — and definitely each time when you hit Open and native OS Finder dialog shows (freezes for more than a minute, a couple of times, then goes back to normal).
Again, the freezing affects the entire system. I'm 99% sure rendering/hardware is not a bottleneck for a bunch of reasons (i.e. the machine runs some pretty heavy AAA games, is able to render complex scenes both on GPU/CPU, does some pretty serious compilation tasks in parallel with sharing screens and video calls, Substance Painter works perfectly, etc, etc) — besides all the nodes render just fine, and, as I previously mentioned, previous versions used to work fine (on this particular machine, since 2017).
This has to be some OS-level call or similar. Based on the symptoms, it _feels_ like it has something to do with file system access — but just in case you'd suspect my SSD, I've ran diagnostics on it as well, and it's completely fine (besides, there's a very slim chance that only a single application would have been affected by a faulty SSD, consistently, even after all the reinstalls). I cannot completely eliminate the OS update as a factor, because I honestly don't remember when I've updated it last time and whether the problem started occurring after that or not. But this has to be something between SD and macOS (the same SD version on Windows works perfectly fine).
I'm running macOS Mojave 10.14.6 (18G103).
PS I've attached a screenshot taken _after_ ~10 minutes of waiting between "Updating Library..." events. You'll see that stats are not even sampled properly by Activity Monitor (and I couldn't switch to any other application either, the entire system is pretty much frozen by SD) as it clearly took a lot more time than what was shown on a spike.
Really hoping we can get to the bottom of this :fingers_crossed: