Given his age and physical condition, Trump could plausibly keel over on his own before his term is up.

It’s also possible that the Dems could retake the House and/or Senate, and even without a veto proof majority, simply refuse to confirm any replacement VP nominee. Doesn’t even have to be related to some desire to see the line of succession get invoked again, there would almost certainly be ample grounds to object to any nominee that Trump or Vance would pick.