While Italy go all-out attack with 4-2-4, Spain seem likely to bench Alvaro Morata in favour of a False 9 approach.
The World Cup qualifier at the Santiago Bernabeu in Madrid kicks off at 19.45 UK time (18.45 GMT).
The latest reports suggest Giampiero Ventura is leaning towards his favoured 4-2-4, pulling Andrea Conti and Matteo Darmian into more traditional full-back roles.
It would enable him to field Lorenzo Insigne, Andrea Belotti, Ciro Immobile, Antonio Candreva and midfielder Marco Verratti simultaneously.
While Italy go all-out attack with 4-2-4, Spain seem likely to bench Alvaro Morata in favour of a False 9 approach.
The World Cup qualifier at the Santiago Bernabeu in Madrid kicks off at 19.45 UK time (18.45 GMT).
The latest reports suggest Giampiero Ventura is leaning towards his favoured 4-2-4, pulling Andrea Conti and Matteo Darmian into more traditional full-back roles.
It would enable him to field Lorenzo Insigne, Andrea Belotti, Ciro Immobile, Antonio Candreva and midfielder Marco Verratti simultaneously.
Mediaset Premium even suggest Leonardo Spinazzola could start, despite not playing for Atalanta this season due to a contract dispute.
Giorgio Chiellini pulled out with a calf injury and is out of action for at least 10 days.
Spain are without Diego Costa, but new Chelsea buy Morata would seem to be on the bench in favour of a False 9 formation.
Coach Julien Lopetegui is ready to make the change so he can get the best out of on form Real Madrid talent Marco Asensio.
He would be supported by Isco and David Silva in a 4-3-3 formation.
Koke so far has the upper hand over Thiago Alcantara in midfield, joined by Sergio Busquets and Andres Iniesta.
Italy need to win in Spain to have a genuine chance of topping the group, and only the winners go through automatically to the 2018 World Cup in Russia.
Finishing second means a play-off and the Azzurri are therefore not holding back tonight.
Probable line-ups
Spain: De Gea; Carvajal, Ramos, Pique, Jordi Alba; Koke, Busquets, Iniesta; Isco, Asensio, Silva
Italy: Buffon; Conti, Barzagli, Bonucci, Darmian; De Rossi, Verratti; Candreva, Belotti, Immobile, Insigne