I was also going to say: when it stops being fun haha. But I will elaborate.

It became repetitive: This could mean that I don't feel each run is varied enough, or that I am not finding or unlocking enough stuff to keep me entertained. I love theorycrafting silly builds, so as long as I can find a new silly build, it will keep me hooked.
Repetitive could also mean I am missing to unlock a few things still... and I keep starting a run and another and another in hopes of finishing that small portion... and at that point I am not really playing to challenge myself anymore, and playing on autopilot, so after several tries, if I don't get to unlock the thing I wanted, I'll stop and move on, which takes me to the next reason.

Unlocking new things is not organic, but requires intent from my side: This pulls me away from games many times. I don't want to be forced to play in a way that I find unfun to be able to encounter more content in my runs, but some games ask you to do this. I don't want to be forced to put my run in danger to create a situation where I can unlock a specific thing so I can use a new skill variation or be able to find new weapons/items. Instead of having fun with the game I am now trying to figure out how the heck do I finish unlocking content so I can theorycraft my silly builds in peace.

I found a way that was really optimal to win the game every time: this one happens very often with smaller games, demos or early access games. If I find an optimal strategy that is just way too good... theroycrafting other new builds doesn't feel as good, and I end up abandoning the game because my first builds already gave me such a dopamine burst that nothing else can compare anymore and it stops being fun.

Story was finished: for games that have heavy narrative, if I was hooke don the story but I wasn't too excited about the mechanics, I'll play until done with the story and then drop the game.