Ideas aren't a problem--original region with lots of wilderness, a variety of pokemon, and the league/local economy is dominated by a megacorporation that makes medicine and bio-tech and is also a leading expert in the biology of various pokemon.
Maybe also the region's source of revived fossils.
(And, since trading isn't an option when the trainers and pokemon are one in the same, something something way to simulate the conditions of a trade that result in evolution.)
Then it's just "what are the major cities like" and "how far into the punk genre do we want to go."
Also where on the scale of anthropomorphism the hybrids are--my preference is that they're human enough to be obviously people but Mon enough that the fact that they'll probably be struggling with having clothes due to a combination of bodily changes and being in the wilderness isn't a big deal.
The problem is getting enough people who want to play it and keeping the game running.