Star of the show at the San Siro was Everton old-boy Wayne Rooney and the Merseysider will no doubt be looking to add to his impressive haul of 21 league goals against the Toffees.
That record is the most of any player playing in the top five European leagues this season, and the in-form hitman has now grabbed 14 goals in his last 13 Premier League games since failing to score against none other than Everton at Old Trafford in November.
After hitting his brace in midweek, Rooney revealed that hard work in training has been the main reason behind his biggest-ever goal haul in a season.
The striker said: "I've been working a lot on getting into the box a lot more, especially inside the six-yard box. That is helping me to score goals, which gives me more confidence."
While Sir Alex Ferguson's side have been in inspired form recently, David Moyes and his Everton team have also been impressing. Indeed, the Toffees have lost just one of their last 11 league games as they look to continue their ascent up the table.
However, considering the fact that Everton have lost 13 times at home to United in the Premier League era, more than any team against any opponent in the competition's history, Moyes and co will be approaching this high-profile fixture with caution.
Indeed, Everton have only won three of the 35 Premier League meetings against United and none of the last nine from which they have taken two points out 27.
If United do manage to get their heads in front, the task facing Everton will be monumental, as, so far this season, the Red Devils have yet to drop a point after going ahead in the Premier League.
Manchester United have no fresh injury concerns, but this match looks to have come too early for Ryan Giggs