The two sides are gunning for their first league title in a decade, and both sit first and second in Serie A respectively.
Both sides clashed in the Coppa Italia quarter final, which Inter narrowly won, a month ago.
Since then, Milan have been going through a somewhat tricky spell, and were comprehensively beaten by Spezia last weekend. They followed this up with a 2-2 draw against Red Star Belgrade in the Europa League.
Milan coach Sfefano Pioli has most of his preferred starting XI available. Gianluigi Donnarumma will start in goal for the Rossoneri. Fikayo Tomori, who played in midweek, is expected to drop to the bench for the returning Simon Kjaer. Kjaer will partner Alessio Romagnoli at the heart of the Milan defence. Theo Hernandez and Davide Calabria will occupy the two full-back positions.
In midfield, Ismael Bennacer is out through injury, so expect Sandro Tonali to replace him. Franck Kessie will partner Tonali.
Soualiho Meite started against Red Star, but is expected to drop to the bench for the titanic clash. Ante Rebic is expected to be brought back into the fold to replace Meite.
Rade Krunic also started against the Serbian side, and he will also drop down to the bench.
Alexis Saelemaekers will be expected to take one of the attacking berths, most likely on the right-hand side. Hakan Calhanoglu will play behind the central striker, with Rebic on the opposite side.
Mario Mandzukic started as the main striker in Belgrade, but he has since picked up an injury, so Zlatan Ibrahimovic will return to lead the line against his old side.
Inter, meanwhile, don't have too many injuries to contend with, as they have no further participation in cup competitions this season.
Antonio Conte has his ideal starting XI to chose from.
In midfield, Conte is likely to continue with the much-maligned Christian Eriksen, whose form has improved in recent weeks. The Dane will likely be flanked by Nicolo Barella and Marcelo Brozovic.
Ivan Perisic will continue as a left wing-back, with Achraf Hakimi on the opposing flank.
Romelu Lukaku, who got into a verbal sparring match with Ibrahimovic in the last derby, will lead the line alongside Lautaro Martinez.
Alexis Sanchez could make an appearance off the bench for Inter, should they need a goal.