Very simplified and basic way of trying to make sense of these things the franchise doesn't give an exact explanation (English isn't my first language so it could be very messy)
So...
Mononokes usually come from the equation people's emotions (really strong ones) + ayakashis
Ayakashis on this sense, as we saw from series and movies, inspired from/are japanese myths and folklore legends. Umibozou, karakasa etc, these all have myths or folklore that align with their designs and powers
They are essentially spirits(/bad spirits if we are following Japanese folklore) that mixed with human emotions, mostly regret, desperation, revenge, or bad emotions.
But
I said usually cause from the series that we also know if they are powerful enough, they don't need a human. Hence, in the series, an ayakashi becomes a mononoke from a piece of wood to lure people. This means sometimes ayakashis venom powerful enough by themselves to take form in the real world
But this may make them less powerful in the human world than other mononokes who are mixed with human emotions. (From the series, the wood piece itself wasn't that strong and used humans it had lured to protect itself and compared to other episodes, the mononoke had lesser appereance and effect)
If a mononoke manages to full form, that means the world is doomed. So, medicine sellers come to existence to balance the things out.
Since the show itself many times referenced folklore and myths, it's possible to assume medicine sellers also come from one. (but that's a post for another time.)
Back to mononokes, their real forms exist in another realm, that's why shingis (the spirits in the exorcism swords) exist and have to slay mononoke in that world. It's another reason for medicine sellers to learn their form, truth, and reason.
But how are they in the human world if their original self is in another realm?
Its because their power reflects to human world from these emotions they are mixed with, and follows these emotions after they managed to reflect to human world (for revenge, escape reality, or lure, etc, as we see in series and movies)
Hence why it's dangerous for a mononoke to take form in human world. If they do, they have to be slain in two worlds, and since shingis probably cant leave that realm and its impossible for humans and even medicine sellers to take them down, its seen as catastrophic. (This leans slightly more to theory again since the show doesnt give an explaination other than "oh we would be doomed if it ever happens")
Now, this part is a bit more of a theory than canon. Usually, the person the emotions come from is dead. We saw in karakasa that the spirit itself, it maybe cause ayakashis look for humans they can manipulate. (From karakasa, it was the umbrella that led kitagawa to her death while she was in a vulnerable mindset)
It is possible that ayakashi searches for strong emotions or vulnerable minds to launch onto and then take a form in human world. All this to try and slip into human worlds. We still don't know why they try, but in most basic theory, it's to feed on humans.
On this theory, we can take ayakashis are like stuck in one room of the house and always trying to find a way to slip into other rooms and destory the house.
In summary they search for a vulnerable mind or strong emotions such as revenge or rage to try and slip into human world, in rare instances they are strong enough to latch onto objects and take a form from that
Thank you for reading my rant, it can be wrong how I interpreted them since the show still has so much mysteries unsolved
