Inter must rely on Romelu Lukaku and Marcelo Brozovic as they try to recapture second place and end a remarkable run of seven consecutive victories for on-form Fiorentina.
It kicks off at San Siro at 17.00 UK time (16.00 GMT).
The Nerazzurri are still fuming after their contentious 1-0 home defeat to Juve before the break for international duty and now prepare for a packed April that includes the Coppa Italia semi-finals and Champions League quarter-finals.
Hakan Calhanoglu, Milan Skriniar and Federico Dimarco are out of action, with Danilo D’Ambrosio suspended following his red card after the final whistle against Juventus for a row with Leandro Paredes.
Lukaku scored four goals in two games for Belgium during the break, a hat-trick against Sweden and a strike in the 3-2 friendly win over Germany.
With so many games coming up, Lautaro Martinez is rested in favour of Joaquin Correa.
Fiorentina have won their last seven consecutive matches in all competition and they too will be busy, going into the Coppa Italia semi-final with Cremonese and Conference League quarter-final against Lech Poznan.
Luka Jovic and Alfred Duncan are out, with Salvatore Sirigu sidelined until the end of the season with a torn Achilles tendon.
Like Lautaro Martinez, Nico Gonzalez is rested after the flight back from Argentina, but Giacomo Bonaventura returns to support Arthur Cabral.
The Viola have not beaten Inter since a 5-4 thriller in Florence in April 2017, followed by five draws and eight defeats in all competition.
When they met back in October, it was an epic 4-3 victory for the Nerazzurri, decided by Henrikh Mkhitaryan deep into stoppages.
The last time Fiorentina won at San Siro against Inter was 4-1 in September 2015.
Inter: Onana; Darmian, Acerbi, Bastoni; Dumfries, Barella, Brozovic, Mkhitaryan, Gosens; Lukaku, Correa
Fiorentina: Terracciano; Dodo, Martinez Quarta, Igor, Biraghi; Castrovilli, Mandragora; Ikoné, Bonaventura, Saponara; Cabral
Player statistic
53' | Giacomo Bonaventura | |||
58' | Gaetano Castrovilli | |||
76' | Jonathan Ikoné | |||
Marcelo Brozovic | 77' | |||
79' | Sofyan Amrabat | |||
Francesco Acerbi | 90+4' |