Inter know a win against Viktoria Plzen would eliminate Barcelona and guarantee their Champions League Round of 16 spot, so Edin Dzeko partners Lautaro Martinez, with Romelu Lukaku on the bench.
It kicks off at San Siro at 17.45 UK time (16.45 GMT).
The Nerazzurri had started the group badly, but got back on track with their 1-0 home victory over Barcelona and 3-3 draw at Camp Nou.
Those results mean a victory here will be enough to secure their ticket to the knockouts, sending Barca into the Europa League regardless of tonight’s meeting with Bayern Munich.
Marcelo Brozovic is the only remaining injury absentee, as Lukaku is on the bench for the first time since the thigh strain at the end of August.
The Belgian has not featured at all in the Champions League since his return on loan from Chelsea.
Viktoria Plzen are bottom of this group on zero points, scoring three goals and conceding 16.
The Czechs also have injuries to deal with, missing Jan Sykora, Jan Kliment and Jan Kopic.
Inter: Onana; Skriniar, Acerbi, Bastoni; Dumfries, Barella, Calhanoglu, Mkhitaryan, Dimarco; Lautaro Martinez, Dzeko
Viktoria Plzen: Stanek; Havel, Pernica, Hejda, Tijani; Kalvach, Bucha; Jirka, Vlkanova, Mosquera; Bassey
Ref: Ekberg (SWE)