crazaghtjyksud.

Great idea, and great mechanics. It has really good/fitting graphics.
The soundtrack and writing both range from good to awesome.
But I think the design and balance are just not fun in the end, and that's not something you can avoid.

First of all, and most importantly: the amount of mindless clicking you have to do is ridiculous. And that's the overwhelming majority of your actual gameplay.
There's no automation or multiple selection; even when you have to manage hundreds of humans, you have to move them one by one. You also have to do this relatively fast, as you can't move humans while paused.
I wouldn't be surprised if this even made the game unplayable for some people, especially with CTS.

There's little to no meta progression in the game, which I didn't expect looking at the Steam page.

The default difficulty is just too high. I will personally do even Hardcore, to have the game 100%, but otherwise the game's difficulty is just not worth for what it offers.
Here I use difficulty for lack of a better word, I mainly mean low chance to win.
When difficulty is offset with progression and/or skill gain, then it can be satisfying. E.g. the overwhelming majority of people won't win Hades or Tainted Grail: Conquest on first try, but there's progression to motivate you. In hardcore games like the old Prince of Persia it feels great to win, because there's skill involved. But in Despotism 3K you rely on random events, and on knowing exactly how to react to those events (to be clear, your reaction is a few clicks at max).
I'm talking about events like ones that either do nothing, or disable one of your 3 crucial facilities for a significant amount of time. The only"skill" in this game is having already encountered a specific event and knowing exactly which option to choose, it's not exactly satisfying. Nor is the game hard to master, despite what the steam page says.

I don't think any of these issues by themselves would be a problem, but combined they seriously affect gameplay experience, constantly and unavoidably.