The End Game is something that all campaigns need. I’ve seen more games fizzle out because there just wasn’t enough drive to keep them going, but there were a few core players who just wouldn’t let them die.
Every character in a setting has their own story, but the setting itself also has a story. A great example of this is the ballsy thing that White Wolf did in around 2002-2004, where they said that since the World of Darkness was the story of a decaying world in the final death spasms before apocalypse, they’d just write a series of books to conclude the game line. I didn’t like it at the time, because some of my favourite games were seeing a conclusion, but I respect the decision to end things on a high. It’s a bit like the re-iteration of D&D versions. A new set of rules comes out and the existing settings either get a reboot or disappear completely (maybe returning when a new version appears a few years down the track).
Know your end point. Know when your setting is about to jump the shark, and stop before you take off. Unless you want your story to go in that direction, in which case go ahead… but you’re on your own from there.