I dunno, I never thought it was difficult to understand.
Some years ago a gate to another dimension opened, New York was destroyed and fused together with that dimension, creating Hellsalem's Lot, a city where humans and monsters live together and all kinds of whacky and crazy shit happens all the time.
Leonardo and Co. are constantly caught up in all that chaos and fight against bad monsters, the strongest of them being the Blood Breeds.
Leonardo has special eyes.
That's basically everything you need to know, the constant chaos is just something that exists but doesn't need to be thought about too deeply
Except blood breeds are ignored after episode 8 or 9.
The dialogues are too vague too.