The important difference is that the Exit Guide feature will search for POIs off Interstate Exits, allowing you to quickly exit and return to the highway. Exit Guide POIs are confined to six categories, Food, Gas, Lodging, Rest Areas, Auto Service, and Shopping.  

The POI on Route feature searches anywhere along your route—it doesn’t have to be an Interstate—and while POIs are chosen for their nearby proximity to your location, they won’t necessarily be immediately accessible upon exit from your route.