There are 2 main airports you can fly to. Rome Fiumicino (near Rome) or Amerigo Vespucci Airport (near Florence). They're both roughly 2 hours away from Spello by car.
You can rent a car at any major airport or in the city. Distance from Rome: https://www.rome2rio.com/map/Rome-Airport-FCO/Spello Distance from Florence: https://www.rome2rio.com/map/Amerigo-Vespucci-Airport-FLR-Via-del-Termine-Florence-Metropolitan-City-of-Florence-Italy/Spello
If you’re not interested in driving, there’s even a direct train from Rome to Spello Italy that takes just under 2 hours, although you will then need to call a taxi to drive you from the station into town. Italy has 2 main train lines: Trenitalia and Italo. Trenitalia is a good choice for extensive routes, especially to smaller towns and rural areas, while Italo is generally a more budget-friendly option with modern trains that exclusively serve major cities. For high-speed travel between major cities, both are comparable in comfort and cleanliness, so the best choice often comes down to schedule and price.