This hasn't been a realistic outcome since the 2000s. Gore or Kerry could have won without any of the former Confederate States, but they both needed MD/DE (which are included in the broadest-allowable definitions of the South.)
Major parties being locked-out of entire regions of the country is very rare. Besides the landslides of the 1970s and 1980s, it only happened to the GOP in the Northeast from 1992-2012 (excepting NH in 2000.)
Bush did win without a single Northeastern state in 2004, but that’s the most recent time a presidential candidate won an election while losing an entire region of states, and I pretty much agree with you that it’s not likely to occur again for a while. Maybe Trump could plausibly win the Electoral College without Pennsylvania; If he’s losing PA, presumably he’s losing every Northeastern state. But of course people would claim that it doesn’t count, because of the ME-2 EV.
Raising ME-2 makes a good point - this is all made up. Even when the GOP was locked out of the Northeast for 20 years, they won 10s of millions of voters there. This is true for both parties in every region of the country going back for ~80 years now. The Solid South hasn't been a thing since the '40s.
