Though head coach Roberto Mancini has managed to maintain his team's 11-match run without conceding a goal throughout the first three games, his defensive plans are once more likely to be disrupted by injury.
Inspirational captain Giorgio Chiellini was forced to train separately from the rest of the squad for much of the week, so may not be risked at Wembley. The Juventus stalwart missed the 1-0 win over Wales, having limped off early in the victory over Switzerland with a muscular problem.
Also an absentee at Stadio Olimpico, regular right-back Alessandro Florenzi has since been confined to rehab in the gym and will almost certainly miss out. Mancini will therefore field Napoli's Giovanni Di Lorenzo ahead of Rafael Toloi - who started in a much-changed XI last time out - on the right of the Azzurri back four.
There will also be a conundrum of a different kind to resolve in midfield, as PSG playmaker Marco Verratti finally returned from a troublesome knee injury last weekend, but Manuel Locatelli scored twice while starring in the first two group fixtures. It seems certain that only one will start in the engine room, with both Nicolo Barella and recent Champions League-winner Jorginho already guaranteed their berths.
Up front, Federico Chiesa, Andrea Belotti and Federico Bernardeschi should make way for the familiar attacking trio of Ciro Immobile, Domenico Berardi and Lorenzo Insigne, though Chiesa impressed against Wales and will be introduced at some point in the second half on Saturday.
Atalanta midfielder Matteo Pessina is another candidate to help change the game if the Austrian defence proves difficult to unlock, after he scored the winner with a deft flick last weekend.
Italy possible starting lineup:
Donnarumma; Di Lorenzo, Acerbi, Bonucci, Spinazzola; Barella, Jorginho, Verratti; Berardi, Immobile, Insigne