Okay first, this wouldn't work due to the amount of fire power we humans have, so in order to work we need to make an environment conducive to supporting a population of deadly megafauna. Here is how that can work maybe:
Step 1: Pull a Dougal Dixxon: Alright so here is the jist? You know how like we humans are smart and shit? Yeah lets rob that from ourselves, lets make some hand wavy nanomachine virus that reorganizes the human geonome structure to turn us into post human monstrosities of <PERSON> After Man. Basically what happens is the grey matter in your brain expands making your brain bigger. Now I bet your like "but wait wouldn't that make us smarter if we got bigger brains" and to that I say "You buffoon no!". If the brain is too large, neural signals have to travel farther to relay messages through out the brain, making our thought processes slower, soon this would reduce us to nothing more than bipedal animals that grunt and hiss. We'd loose our ability to plan and communicate and simply rely on our instincts. Couple this with the ability to make the nano virus change the human body to adapt to certain climates better and you have a new species of weird post human monsters. You can have ghouls with bow legged feet that bite people and turn them into ghouls. You can have tundra ogres or real life mermaids, or some hive mind ghoul swarm. Make the virus highly contagious and immune to vaccines and release the virus in as many places as possible to spread it as quickly as possible. These aren't like your regular zombies, these are post humans, they can adapt, survive, eat, and procreate via normal sex to produce more ghoulish offspring, they don't necessarily have to bite people. 335
They are social pack hunting animals adapted to killing large prey or humans (maybe they are still intelligent enough to trick people by wearing clothes or ambushing them by mimicing baby cries)
Step 2: Now this is where the fun begins: Okay so you got your hordes of humanoid aberrations but you think thats it? HAHA no this is the part where you are free to release whatever havoc you want to release upon the human race. This part is up to you, you can make a whole ecosystem of dinosaurs that claim the urban spaces once occupied by humans which would make it extremely difficult to reclaim, But honestly I think the best solution is just mutate regular vermin, giant mutated rats, monitor lizards, and especially bugs. Maybe reprogram your post humans to adapt to these new deadly vermin megafauna and learn to avoid them or intimidate them. Some good inspirations for giant vermin would be games like Rain World or web comics like HIVE. HIVE is basically about climate change releasing so much CO2 into the air that it mutates wasps and turns them into like bear sized wasps that build giant paper nests on skyscrapers. They are like the Starship Trooper Bugs fused with Xenomorphs. They can create disturbing human zombies infected by wasp larvae or straight up bug centaurs. Rain World takes place on an alien planet once ruled by a dominant ancient civilization that offed itself thousands of years ago, now the animals they saw as vermin and pests roam free in their ancient ruins, you got cybernetic vultures, neon lizards, intelligent minks and primates capable of carrying tools around, flying centipedes and squid bats, pole plants and monstrous kelp that will eat you. Also Love Death and Monsters does a similar thing where an apocalypse causes cold blooded animals such as invertebrates, reptiles, fish, and amphibians to grow to the sizes of cars and kill and eat everybody.
Conclusion: Ta-DAH now you got a post apocalyptic world crawling with sub-human mutants and giant vermin. You can hand wave this all because maybe the mad scientist villain really likes monster movies and was wronged in the past or something and wants to get back at humanity by bringing the monsters they feared to life. Make him like an immortal cyberlich with nanomachines and clones that can regenerate himself but give him one big weakness or something.
Bonus Tip: If it seems to unrealistic as to how all these creatures would coexist, make drones or robots that monitor the ecosystem. Something AKIN to horizon zero dawn or breath of the wild with robot animals or guardian mechas that are self sustaining and autonomous able to collect data on its ecosystem and making sure the wildlife doesn't get too out of control. 238