Mosters loot is fix or random?
Monster's loot is fixed, in that they will always only drop certain types of items, and there aren't any "rare drops". But they don't always drop common items, either. For example, a snail won't always drop a snail slice.
It is also fixed in that some monsters drop special items. But this is pre-scripted (part of puzzles/challenges), and you aren't going to repeatedly be able to kill a monster that will drop the special item.
Do monsters respawn?
Not unless you're moving.
I've mapped out at least a few static triggers where if you walk over the specific spot on the floor a monster will spawn. But if you don't walk over that tile, and you've cleared it out, the room is perfectly safe to sleep in.
In fact you can even sleep on the trigger. It waits for you to walk onto it to fire, rather than simply detecting your presence. They won't spawn a monster every time you walk over the tile, though, because they have a cooldown before they reset.
This is important to me to understand if I can safely rest
Sometimes it is hard to tell if there are still enemies, as they don't all immediately home in on your location. Also, some monsters are harder to detect than others. You'll get a sense for this as the game progresses and you get more familiar with each monster.
There are often safe rooms you can lock yourself in, as monsters generally can't open doors.