While the hosts are battling for Champions League qualification, the visitors need nothing short of a miracle to avoid relegation from the top flight.
Match preview
AC Milan extended their unbeaten run in all competitions to seven matches after playing out a 1-1 draw away against Roma last weekend - their third draw by that scoreline in their last four games.
The contest in the Italian capital was goalless heading into stoppage time until Tammy Abraham netted what appeared to be a 94th-minute winner for the hosts, only for Alexis Saelemaekers to go up the other end three minutes later to score a dramatic equaliser and rescue a point for the visitors at the death.
Stefano Pioli's side, who are on the cusp of handing over their Scudetto title to Napoli, have slipped out of the top four and down to fifth place in the table, albeit on goal difference after rivals Inter secured a 3-1 win over second-placed Lazio.
Milan are now preparing for three successive home matches to begin the month of May, with back-to-back Serie A home encounters with Cremonese and Lazio followed by the first leg of the Champions League semi-final with bitter rivals Inter in a weeks' time.
The Rossoneri have put together a seven-game unbeaten run at San Siro, keeping six clean sheets in the process, and they will be hoping to have more joy in front of their own fans on Wednesday against a Cremonese side whom they thrashed 7-1 in their last top-flight home meeting back in May 1996.
After losing 2-0 on aggregate to Fiorentina in the Coppa Italia semi-finals, Cremonese were forced to play out a 1-1 Serie A draw at home against relegation rivals Hellas Verona on Sunday.
The Grigiorossi took the lead courtesy of a ninth-minute strike from David Okereke, but the second-half sending off of Giacomo Quagliata proved costly as Verona fought back with an extra man to claim a point, with Simone Verdi netting a 75th-minute equaliser.
Despite edging a point closer to 17th-placed Spezia, Davide Ballardini's side remain 19th in the table and sit seven points adrift of safety with just six Serie A matches remaining, and hopes of survival are slim considering four of their final six fixtures are against teams sitting in the top eight.
Cremonese have picked up as many points on the road (10) as they have on home soil (also 10) so far this season, with four points accumulated in their last three away games.
The Grigiorossi can also take confidence from the goalless stalemate played out with Milan on home soil in November, and another resilient performance will be required if they are to claim a positive result on Wednesday.
AC Milan Serie A form:
L
W
D
D
W
D
AC Milan form (all competitions):
D
W
D
D
W
D
Cremonese Serie A form:
D
L
W
W
L
D
Cremonese form (all competitions):
L
W
W
L
D
D
Team News
AC Milan centre-back Fikayo Tomori is a doubt after coming off at half time against Roma with a hamstring injury, while Alessandro Florenzi, Zlatan Ibrahimovic and Tommaso Pobega all remain in the treatment room.
The potential absence of Tomori could see either Malick Thiaw, Pierre Kalulu or Matteo Gabbia handed a start in central defence alongside Simon Kjaer, while Davide Calabria and Theo Hernandez are expected to continue at full-back.
Pioli may consider rotation in midfield and attack considering Milan's busy fixture schedule, with Saelemaekers, Junior Messias, Ante Rebic and Charles De Ketelaere among those pushing for a recall.
As for Cremonese, Quagliata is suspended following his red card last weekend, while Marco Benassi and Frank Tsadjout are set to miss out again due to injury.
Vlad Chiriches returned to the matchday squad against Verona after recovering from injury and could be selected to start at centre-back alongside Johan Vasquez and Luka Lochoshvili if Ballardini decides to select a back three.
Okereke, Daniel Ciofani and Cyriel Dessers are Cremonese's joint-top scorers this season with six goals each, and the attacking trio will battle for a place up front, with the former two hoping to retain their starting spots.
AC Milan possible starting lineup:
Maignan; Calabria, Kjaer, Thiaw, Hernandez; Krunic, Tonali; Saelemaekers, Bennacer, Leao; Rebic
Cremonese possible starting lineup:
Carnesecchi; Sernicola, Vasquez, Lochoshvili; Valeri, Pickel, Castagnetti, Meite, Buonaiuto; Okereke, Dessers
We say: AC Milan 2-0 Cremonese
Cremonese are running out of games to pull off a miraculous revival and they know that anything but a win on Wednesday will put them on the brink of relegation.