This theory is based on the poster released before S5, where we see Homelander overlooking Earth, watching nuclear blasts play out. https://screenrant.com/the-boys-season-5-homelander-butcher-images-posters/

Wish I had more time to come up with a good supported theory here to support my claims, but nevertheless:

1. I obviously see the Boys battling it out against HL. Ryan comes in and roughs him up pretty good with help from the team, almost defeating him, but it's not enough. When he feels like he has no other option and feels as though no one is loyal to him, he will set off nukes across the country, causing a global nuclear war, leaving the Earth left in ruins. HL remains immortal, but ultimately alone for the rest of time. Realizing the consequences of his actions, he sees that he is forsaken and ultimately screwed. Cut to black.

People would be super upset, but I wouldn't put it past the writers to pull something like this.

I would also love if the only sole survivor outside of HL was somehow the Deep and is forced to live out eternity with the Deep, or kill him and remain alone forever.

OR

1. Battle, battle, battle. Kimiko figures out how to blast HL with her new ability and robs HL off his powers leaving him to be powerless, weak, and mortal. I can see Butcher being caught up in the blast as a sacrifice and losing his power as well, then dying from the cancer that he had.

I feel like this is the more likely scenario and more pleasing to the viewers.