Giacomo Raspadori is the favourite to start as a centre-forward, with Jorginho and Federico Chiesa, while Federico Gatti steps in for injured Alessandro Bastoni when Italy host North Macedonia.
It kicks off at the Stadio Olimpico in Rome on Friday at 19.45 GMT.
The Azzurri need four points from the remaining two games against North Macedonia and Ukraine to secure qualification for EURO 2024 and avoid the play-offs.
Coach Luciano Spalletti has been forced to do without several players who pulled out through injury, including Bastoni, Manuel Locatelli, Mateo Retegui, Davide Calabria, Rafael Toloi, Cristiano Biraghi and Giorgio Scalvini.
This limits the options in defence, so Juventus centre-back Gatti steps into the all-Inter group of Matteo Darmian, Francesco Acerbi and Federico Dimarco, as Giovanni Di Lorenzo is suspended.
Jorginho had not been called up since the Nations League Final Four, but goes straight into the starting XI for his first cap under Spalletti.
Raspadori is the favourite to be a centre-forward rather than Gianluca Scamacca, flanked by Chiesa and Domenico Barella.
Probable line-ups
Italy (4-3-3): Donnarumma; Darmian, Gatti, Acerbi, Dimarco; Barella, Jorginho, Bonaventura; Berardi, Raspadori, Chiesa
North Macedonia (3-5-2): Dimitrievski; Manev, Serafimov, Musliu; Ashkovski, Elezi, Atanasov, Bardhi, Alioski; Elmas, Miovski