The fixture is one of the most hotly contested derbies in world football and, while neither side is challenging for the title, there is still a lot riding on the outcome.
Milan, the designated home team for the Serie A clash at San Siro, head into the encounter as perhaps the side most in need of the points, having endured a largely forgettable campaign.
Clarence Seedorf's charges are in 10th position, an incredible 42 points adrift of leaders Juventus, having lost 12 times in Italy's top flight this season.
Yet, there may still be a positive end to the season, with a UEFA Europa League berth within their reach.
European qualification had looked unlikely until a five-match winning run preceded last Friday's 2-0 defeat at high-flying Roma, but Milan remain just one point adrift of sixth place.
That is likely to yield a spot in Europe's secondary competition as Coppa Italia finalists Napoli and Fiorentina are all but certain to qualify for continental competition courtesy of their league positions.
However, if Milan are to boost their hopes they will need to improve on recent performances in the derby, having failed to win any of the last five league clashes - Inter winning four of those.
Breaking that recent hoodoo will be no easy feat against an Inter side who have lost just once in their past 13 Serie A matches.
The biggest problem for Walter Mazzarri's men this season has been too many draws, with no team in Serie A having registered more than Inter's tally of 15.
That has prevented Inter from challenging for the title, or even a spot in the UEFA Champions League but, after a ninth-placed finish under the stewardship of Andrea Stramaccioni last term, Inter have shown signs of progress.
A place in Europe could be confirmed with three points and, with ambitious owner Erick Thohir ready to invest to improve the playing squad, a return to the Champions League may be a realistic prospect next season.
Inter, who were indebted to Rodrigo Palacio for his late winner in December's reverse fixture, welcome back defenders Rolando and Walter Samuel from one-match bans.
Milan forward Stephan El Shaarawy is hopeful of making his long-awaited return after a season plagued by a troublesome foot injury.
