The first hurdle is a workable PoD. To be sure, the issue of isolationism vs. interventionism appeared to be coming to a head in the 1940 presidential election--that is, until Willkie prevailed (mercifully, IMO) and make interventionism essentially a given. So, the first order of business would be either a much stronger "no third term" coalition among Democrats or a much stronger "stop Willkie" coalition among Republicans, or both. I suspect the latter is more feasible (notice I didn't say "easier").
Let's assume that Willkie, who died in 1944, and was known to be something of a chain smoker, died in early 1940 before the convention. At that point the rest of the GOP field was decidedly more diffuse, with Taft, Vandenberg and Dewey as the front runners--and Hoover waiting in the wings ready to volunteer in case of a deadlock. All were isolationist to some degree.
OK, so somehow the personality-challenged Taft gets the nomination, and perhaps chooses a young (38 at the time) Dewey as his running mate. If somehow Franklin Roosevelt made his case for a third term to the Dems, he should have little difficulty in turning Taft inside out in three states where it really counted in those days (NY, PA, IL) given the hefty labor presence in all three states and major city machines (aside from Philadelphia). Add to that the eleven ex-Confederate states and Roosevelt has 236 electoral votes right there. I'll stipulate he'd likely lose OH, IN, MI (the Vandenberg influence) and the Plains and Mountain states (hotbeds of isolationism). But people were already getting nervous about the Japanese on the Pacific coast, so I'd suggest CA, OR, and WA will go for Roosevelt. That boosts him to 271, putting him over the top.
You'd need a couple of major gaffes (maybe Henry Wallace putting his foot in his mouth a few times?) to get Taft anywhere close--that, and a lot of luck. Willkie was charismatic and electrified people yet he still lost substantially; Taft was about as bland as they come. And I say all of this as a lifelong Republican.