The Azzurri have limited attacking options for matchday six, as both Ciro Immobile and Mattia Zaccagni are out with injuries, while Gianluca Scamacca and Federico Chiesa should be spared for next week's trip to England.
As such, Giacomo Raspadori will likely operate at the tip of Spalletti's attack, with Moise Kean and Domenico Berardi also aiming to terrorise the leaky Malta backline.
Euro 2020 winners Marco Verratti and Jorginho are nowhere to be seen either - the same goes for Lorenzo Pellegrini - so Manuel Locatelli and Nicolo Barella will expect to hold their spots in the engine room.
Sandro Tonali has quickly made a name for himself at Newcastle United, but owing to his game-winning brace against Ukraine last month, Davide Frattesi could get the nod in the centre of the park again.
Tottenham Hotspur duo Destiny Udogie and Guglielmo Vicario represent the only two uncapped players in the squad, but the former is expected to play second fiddle to Federico Dimarco at left-back, while Gianluigi Donnarumma's spot in goal is not under any threat.
Alessandro Bastoni and Gianluca Mancini seem set to pair up in front of the Paris Saint-Germain number one, while Matteo Darmian may start at right-back, allowing Giovanni Di Lorenzo a breather.
Italy possible starting lineup: Donnarumma; Darmian, Mancini, Bastoni, Dimarco; Barella, Locatelli, Frattesi; Berardi, Raspadori, Kean
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