This will be the first time the two European giants have met since 2010 when Man United swept their Italian opponents aside with a 7-2 aggregate win in the Champions League.
While they do not meet in Europe's most elite club competition this time, both sides are enjoying positive seasons and this looks set to be a tightly-contested affair.
Here is how the two squads could enter this game.
There will be some tough decisions for Solskjaer to make with doubts surrounding the fitness of a number of key players. Edinson Cavani missed the Manchester derby having aggravated an injury in training while Donny van de Beek has not featured in the past five games and the latter has been ruled out.
Dean Henderson will keep his place between the sticks with David De Gea still in Spain following the birth of his child. Meanwhile, Paul Pogba, Juan Mata and Phil Jones are still expected to be out for some time.
More worryingly though, Marcus Rashford limped off against Manchester City and although a scan did not reveal any serious injury, his ankle is said to be swollen, making him a doubt for Thursday's match.
The Rossoneri are in a similar position when it comes to injuries with question marks over the availability of several important players. Former red Zlatan Ibrahimovic has been ruled out. The 39-year old picked up a thigh injury in last week's win over AS Roma and will be a huge miss given his 14 goals in 13 starts this season.
As well as the veteran Ibrahimovic, Milan are also without a further six first-team players who were absent for Sunday's 2-0 win against Hellas Verona. Ante Rebic, Daniel Maldini, Hakan Calhanoglu, Ismael Bennacer, Theo Hernandez and Mario Mandzukic all occupied the injury list for that most recent Serie A fixture and have not been included in the travelling squad.
United: Henderson, Wan-Bissaka, Bailly, Maguire, Shaw, McTominay, Fred, Greenwood, Fernandes, James, Martial.
Milan: Donnarumma, Calabria, Tomori, Romagnoli, Dalot, Kessie, Tonali, Castillejo, Krunic, Saelemaekers, Leao.