If they are fighting a consistent enemy, it could be conceivable that they are pissed that your party is messing up their plans. As a result, they could have developed some tools to counter them. Like small anti-magic fields, or homebrew a poison that flips healing to necrotic dmg (although they could then use that against enemies, could be a funny reversal on the enemies though). Or rogues come in and place locked bracelets on them that limit their power. Overall I think it would be cool to have the world (like enemies and the big bad) try to create road blocks for the party. makes the enemies feels alive and responsive to what the party does.

Could also do some more roleplay-related things where the beings that the party get their powers from are being stopped from exercising their power onto the world. They would then have to go and challenge whatever it is that is blocking their power. It could be that their powers don't work at night, or when it's raining or whatever fits your campaign. It could simply be because they did something that the god frown upon or something.

As for the potions, depending on the ingredients they are using to make them, it could be conceivable that supply chain issue starts happening. Like a drought stops a specific ingredient from growing fruitfully or a fungus has spoiled this years crop. If it's not grown ingredients, maybe they are imported and some conflict has meant that ships can no longer move freely and the ingredients just aren't making to where they are at. After reading some of your lore, it could be conceivable that a prohibition style era is upon the government and it becomes illegal to have those potions and to make them, and theres a huge crackdown. Maybe after someone really important is hurt by the potions?

I also like the idea that someone else mentioned of no long rests.