Defeated candidates have managed to end up winning the White House (Nixon lost being Governor of California, and then won the Presidency). Abraham Lincoln ran and lost for Senate, and then won the Presidency.
If the Republicans run Trump (or a fanatic MAGA isolationist), and the Democrats run Biden (or even better, run an enthusiastic WOKE candidate), there will be an opportunity for a third party founded by the “ruins” of the moderate wings of the Democratic and Republican parties. Cheney and Romney (and perhaps Collins or Murkowski) are possible founders of a new party. McMullin if he wins a Senate seat would be a very strong possibility. Among Democrats, candidates, or at least founders, of a third party would include former Senator Lieberman, Manchin and perhaps Tulsi Gabbard from Hawaii.
For a third party to win, both the Democrats and Republicans have to move to radical extremes. The third party doesn’t need to win a majority of electoral votes, but only enough to force the election into the House of Representatives where being the second choice of both parties would be enough to win.