Fatima to Seville

According to Rome2Rio take a bus from Fátima to the Lisboa – Oriente station in Lisbon.
Take the subway from the Oriente station to the Vermelha – Aeroporto station.
Fly nonstop from Lisbon (LIS) to Sevilla (SVQ). The further out you buy your ticket the cheaper it is.

Your choices are drive, fly or take the bus.
From Fátima you can take Flixbus to Seville with a transfer in Lisbon.
It's a very long ride around 9 hours, if I was doing it I would take the night bus and sleep .
https://shop.flixbus.pt/

The other bus option is Redeexpressos, take a bus to Faro and then a bus to Seville.
Even longer than the Flixbus.
https://rede-expressos.pt/en/timetables

Driving would probably be very costly if you rented the car in Portugal and returned it in Spain.