Mutated packs of zombies might be interesting, similar to champion packs in Diablo. You could even go so far as to give them hard-immunities to certain types of damage, particularly as the game continued.
I was thinking seasonal difficulties might provide a bit of flavor for late-game.
Your first couple of seasons would be normal, but after winter had passed, each season would have a chance of being abnormal (severity depending on how long the player has been alive for).
Some example effects:
Random fires occuring during the day.
Volcanic activity / aggressive magma flows.
Meteor strikes replacing lightning storms.
Heat haze, massively reducing weapon ranges.
Energy activity resulting in random zombies being accelerated.
Radiation waves of increasing intensity. The closer you are to the surface / outdoors, the higher the exposure. (forcing the player to survive underground in part)
Scorching UV, damaging the player if he is uncovered or not wearing thick enough protection.
High friction air, where ordinary ballistics become highly ineffective or unpredictable.
Nuclear winter, a permanent snowstorm where moving outdoors would be much slower and difficult.
Icicle spores popping up from the ground like splinter mines. Individually not threatening, but walking on them creates sounds that monsters might hear.
Frost, giving guaranteed moments where your vehicle will lose control as well as poor/no plant growth.
Ice mutation, all outdoor zombies inflict a stacking slow when they hit players and vehicles (regardless of armor absorption).
Persistent ice storms where you take minor damage outdoors.
Brittle mutation, all melee damage doubled for both parties outdoors.
Crystal air, altering the effect of energy/sci-fi weapons erratically.
Spring/Autumn (perhaps keep these mild so as to give the player a break between rough seasons):
Acid pools bubble to the surface slowly.
Wildlife boon causing wild life to greatly repopulate (and obviously zombify shortly) as well as forests becoming laden with living plants. (forcing players out of their lovely forest resort)
Acoustic resonance mutation, magnifying sound loudness high enough that sneaking is no longer the primary option.
Zombie mutation (less zombies in general, more packs of identical specials)
Marsh weather, causing all grass tiles to be more difficult to traverse, sometimes acting as small holes.
Bacterial storm, explosively damaging bleeding and cut damaged individuals.
Really just the kind of things to force you out of your comfort zone in late-game. Not all effects would have to be a malus, just something to keep things interesting in late game.
Perhaps there could even be long-term quests to eliminate(or increase) certain weather conditions that players could attempt. For instance your game would be seeded with different malus seasons (you’d experience these consistently after the first winter) and you’d work towards restoring the world back to normal (mostly for your own convenience of course), otherwise the effects may intensify beyond your control.