The Wilkie race was a rout, but not quite to the extent Alf Landon had been. Republican strategists could confidently extrapolate that if they kept picking up votes as they had in the last two elections, they could defeat Roosevelt by 1952 or '56 at the latest. This appeared to be about the same time frame when the New Deal would finally solve the Great Depression.
After two Democratic terms, unemployment was still over 14%. It seemed FDR would create programs and shovel out dough, but unemployment would inch down only a little. Then he'd create more programs and shovel more dough, but unemployment still only inched down a little. No one could figure out why this wasn't working. (Fortunately, for some reason or other, in 1942, unemployment suddenly dropped to 4.7%.)
Republicans charged Roosevelt wanted to get us into a European war, but nothing could be further from the truth. Roosevelt sent Joe Kennedy to suss out the situation in Europe, and Kennedy came back with an upbeat, optimistic assessment: "Democracy is finished in Europe, and it may be finished here," so as far as anybody knew, things were hunky-dory. 1
In any case, Roosevelt won the election handily, and Wendell became his unlikely supporter during World War II, serving as Roosevelt's personal representative to Britain, the Middle East, the Soviet Union, and China. 2
Franklin Roosevelt: 449
Wendell Wilkie: 82
1. Some people accused Joe Kennedy himself of being an anti-Semite, but his remarks have been taken out of context. A comment like, "[some] individual Jews are all right... but as a race they stink. They spoil everything they touch" might be taken any number of ways.
2.Wilkie is rumored to have an affair with Chiang Kai-Shek's wife, Soong May-Ling. Not that this has anything to do with being a presidential loser, except to say, "Way to go, Wendell!"