Although the two teams have enjoyed markedly different fortunes this term and 19 points separate them in the table, both sides have plenty to play for as the season rushes to a close.
Milan currently sit just three points behind league leaders Juventus. They would love nothing more than to close that gap against their local rivals.
Internazionale are 20-plus points out of the title hunt, but they are fighting it out with Udinese and Napoli for the final Champions League place. All three teams are on 55 points with three matches remaining.
The Milan derby is always hard-fought, occasionally ugly and often genius. Here are six bold predictions for Sunday's match.
Sometimes Disney movies happen in real life. That's how things are shaping up for AC Milan forward Antonio Cassano.
After falling ill in October and subsequently being forced to undergo heart surgery, Cassano is back months ahead of schedule. And he's back in style.
A goal and two assists in his first full match since returning reintroduced the Cassano threat to Serie A.
He's hungry, he's on form and he's going to score as the first half of the match draws to a close.
Lucio is not a particularly ill-disciplined defender. But this isn't going to be a regular day at the office for the Brazilian.
The 33-year-old leads Internazionale in tackles per game. Against Milan's forward line, one of those tackles is going to go astray early.
Expect Lucio to be forced into a desperation tackle as the back four settles. To show he has control of the derby, the referee will show the defender yellow before the 20-minute mark.
Diego Milito is the danger man for Inter. Everyone knows it. Most of the time, he scores anyway.
But Milito beat Milan in the first derby of the season and the Rossoneri will be loath to let him do it again.
In a game where Inter will see little of the ball, Milito starves and has no impact on the final score.
He's not bad even when he's struggling and he's unstoppable when his confidence is running high. So, Inter fans should be concerned that the big Swede is in the press this week comparing himself to a fine wine. He's definitely breathing his own vapors at the moment.
The game gets to the half with Milan up 1-0. Ibrahimovic strikes twice in the last 20 minutes as a tiring Inter defense gets sloppy in their marking.
With AC Milan's defense focused on keeping Diego Milito off the ball, Wesley Sneijder will find space in front of the Milan defenders.
The Dutchman is brilliant from 25 yards out and he will unleash a few from that range during the derby.
Most will be saved, some will go over. But at least once, Sneijder will strike a curler toward the far corner and see it glance off the crossbar.
Inter are not the most secure defense in Serie A. Milan scores more than anyone else in Italy. One thing is assured, Julio Cesar will have plenty of work to do on Sunday.
Even in their 1-0 win during the season's first derby, Inter gave up 16 shots and ceded two-thirds of the possession to their opponents.
As if to return the favor, Milan were incredibly wasteful and only forced three saves out of Cesar.
Inter's luck will not hold this time around.
At the final whistle, the Rossoneri will walk away with a 3-0 win and extend their pursuit of Juventus for the Scudetto.