The Rossoneri know they only need a point to secure their place in the last 16 of the Champions League, while the Amsterdam outfit must win in Italy to ensure its progression.
AC Milan hosts Ajax on Wednesday in a Champions League showdown to decide who will join Group H leaders Barcelona in the knockout stages.
The home side currently sits two points behind the Catalans and could win the pool should the Spanish champions lose at home against the already-eliminated Celtic.
Ajax, meanwhile, is three points off the top, but cannot climb above Barcelona because of its inferior head-to-head record. However, it will be hoping to avoid conceding its 200th European Cup goal as it goes in search of the three points it needs to reach the last 16 at the Rossoneri's expense.
The Amsterdam outfit came close to a home win against Milan on matchday two, taking a 90th-minute lead through Stefano Denswil before Mario Balotelli equalized from the spot in the fourth minute of stoppage time.
Frank de Boer's men have not won any of their last six away fixtures in the Champions League, dating back to a 2-0 success at Dinamo Zagreb in October 2011, but are unbeaten in their last three matches in Italy.
Milan ended a run of seven games without a win in all competitions when it cruised to a 3-0 win at Celtic last time out, scoring its 600th goal in competition in the process.
After a dismal start to the domestic season, Massimiliano Allegri's side is now unbeaten in four Serie A matches and appears to have turned a corner.
Its Dutch opponents defeated Barcelona 2-1 on matchday five in one of their biggest European results in recent years, and have won their last four matches in the Eredivisie, leaving them second behind Vitesse.
The four-time European Cup winners won 4-0 against NAC Breda in their most recent domestic fixture, and were victorious on their last visit to San Siro, when they ran out 2-0 winners in the 2010-11 Champions League group stages.
Marco Amelia (knee) is expected to be out until the new year, while Mattia De Sciglio (knee), who has made only one appearance since August, is among a number of injury doubts for Milan. Giampaolo Pazzini (knee) is a long-term absentee. Robinho is not expected to be back until the end of the year.
Ajax, meanwhile, is without its captain, Siem de Jong, and defender Nicolai Boilsen, who have both picked up hamstring injuries. Lerin Duarte also has ankle problems, while Joel Veltman is suspended.
However, it welcomes back Icelandic striker Kolbeinn Sigthorsson, who has recovered from an ankle injury he sustained in Iceland's World Cup playoff clash against Croatia.