Inter use almost a full-strength squad with Romelu Lukaku and Alexis Sanchez, while Milan have Brahim Diaz and Rafael Leao supporting Zlatan Ibrahimovic.
The Coppa Italia quarter-final kicks off at 19.45 GMT and will be decided after 90 minutes, extra time or even penalties.
The winners of this tie go on to face either Juventus or SPAL in the two-legged semi-final.
It’s not just a Derby della Madonnina for the Coppa Italia, as these sides are also fighting it out at the top of the Serie A table, with the Rossoneri crowned Winter Champions on Saturday.
Inter have almost a full squad to choose from, missing only Danilo D’Ambrosio, but Lautaro Martinez and Achraf Hakimi are rested, with Aleksandar Kolarov coming in for Alessandro Bastoni.
Milan must do without injured Mario Mandzukic, Sandro Tonali, Pierre Kalulu, Matteo Gabbia, Ismael Bennacer and COVID case Hakan Calhanoglu, while Gianluigi Donnarumma is suspended for the Coppa.
That’s because he was sent off from the bench for protesting during the last round with Torino.
Ciprian Tatatursanu therefore takes the gloves, with Alessio Romagnoli returning to defence after his Serie A ban for the 3-0 defeat to Atalanta on Saturday.
Diogo Dalot allows Davide Calabria a very rare rest.
Soualiho Meite starts again, but this time in midfield, with Alexis Saelemaekers, Brahim Diaz and Leao supporting Ibrahimovic.
The Rossoneri won 2-1 when they last met on October 17, 2020.
This will be their 25th Coppa Italia encounter, with Milan winning 10, drawing seven and losing seven.
Inter: Handanovic; Skriniar, De Vrij, Kolarov; Darmian, Barella, Brozovic, Vidal, Perisic; Lukaku, Alexis Sanchez
Inter bench: Padelli, Radu, Hakimi, Gagliardini, Lautaro Martinez, Sensi, Ranocchia, Young, Eriksen, Bastoni, Pinamonti
Milan: Tatarusanu; Dalot, Kjaer, Romagnoli, Theo Hernandez; Kessie, Meite; Saelemaekers, Brahim Diaz, Leao; Ibrahimovic
Milan bench: A Donnarumma, Jungdal, Calabria, Castillejo, Rebic, Hauge, Kalulu, Tomori, Maldini, Krunic