Pretty sure the TotK hundo route is already around 35-40 hours

Resolutiion could use some glitches, right now it's mostly a walk-fight gameplay loop with one boss skip. Quitting to menu during interactions can cause a useless sort of text storage but nothing useful along the lines of interaction storage exists yet.

Speedrunning a game while on a treadmill... Running while running

I'd be willing to bet that a large % of games do have boss skips. One that immediately comes to mind is Breath of the Wild any% firing an arrow and entering a boss cutscene, so that the arrow continuously damages the boss during the cutscene and kills the first phase.

I've run a lot of Hyper Light Drifter, and in glitched runs, there are so many ways to get out of bounds that only the final boss is required.

I've also found this skip for Resolutiion any% where you can just leave the room while the boss wakes up, interact with the thing he's guarding, then quit back to your last checkpoint

There was a brief moment where a couple Hyper Light Drifter runners (myself included) were doing "any% boss rush escape" as a category. Boss Rush uses the same rooms as a boss normally appears in, with door transitions repurposed. But the Eastern boss room has 3 doors, and the devs forgot to remove the transition on one, so you can clip out of bounds to reach it and enter a room in the Eastern biome with all abilities and upgrades (more than NG+ even!). And then beat the game from there.

It didn't really catch on because the category is quite similar to any% NG+, and also most runners prefer NMG

This isn't quite TSP because you can select which things to visit, but you might be able to set up some sort of Integer Linear Program to solve it (just form a graph of every Thing To Be collected and every doorway, so you can time Item to Item and Item to Doorway in a room. Then reduce it to a complete weighted graph of just the Items. Set a function Value(vertex) for how much progress that item gives you (1/8 for most). Set constraints such that the edges to be included in your route form a path, and you get at least 32 value total. Making it a continuous path instead of possibly some multiple paths is the hard part, not sure what constraints that would require.

Normally, games will have additional restraints about where you can go and when that makes it so that routing is a largely human endeavor and programs aren't necessary, especially given how hard it would be to set this all up. I'm not an expert on integer programming either so even if this would work, idk if it's practical or not.