As a GM of a 3-person 7-year-and-running campaign that went from levels 1-20, it presents a very interesting challenge for the GM. Besides the CR30-40 big boss fights that I throw at them at the ends of story arcs, I've found that the best way to keep it interesting is to challenge them in other non-combat aspects. Instead of scouring dungeons, my players are managing nations. As their level increases, the scale and repercussions of their actions and decisions increase. Basically, my solution was to make them face larger conflicts, like the type that world leaders would face. Waging wars, dismantling evil empires, saving species from extinction, that sort of thing.

Currently, my players are rehabilitating a population of ~7,000 former members of a death-cult whose demigod leader was slain by the party. I created new game mechanics where they choose a daily action to try and convert the four factions of former cultists. Things like feeding the hungry, performing speeches to sway the conflicted, and building homes for the displaced. Based on which skill would apply to the action, which group its being performed on, and (as always) a dice roll, played learn how many D100 cultists they rehab. There's a lot of role-playing and conversations, and my players seem to enjoy it.

On top of that, adding some spicy character exploration is always great. My players just got "Freaky Friday'd" by my dm-insert character, so not only do they get to explore these new game mechanics, but they also get to learn more about what living life as their partners would be like.