With the UEFA Champions League having reached the knockout stages, both sides will be dreaming of lifting the trophy in Rome on 27th May.
However, that ultimate goal remains some way off, with an intriguingly poised contest at Old Trafford representing the next hurdle for these European heavyweights.
A goalless first leg at Giuseppe Meazza a fortnight ago has ensured that the return fixture has become a make-or-break battle of epic proportions.
United, who will looking to stretch their 20-game unbeaten run in continental competition, are past masters at grinding out results when the stakes are high and victory by any margin would be enough to see them through.
Inter, meanwhile, know an away goal would put them in the driving seat as Jose Mourinho looks to mastermind another memorable triumph over his old adversary Sir Alex Ferguson.
The Portuguese coach boasts an enviable record against his Red Devils counterpart, losing just once in 13 meetings, but his current charges have struggled against English opposition down the years.
Inter have failed to win any of their last five meetings against Premier League sides in the knockout stages of the Champions League, while their last visit to Old Trafford, in 1999, ended in a 2-0 defeat.
With United having kept a clean sheet in seven of their last nine outings in the competition, and still on course to claim an unprecedented quintuple, the Italians could be in for more misery in midweek.
Welcome returnFerguson's cause has certainly been boosted by the news that Rio Ferdinand is fit enough to take his place at the heart of United's defence.
The England international had been a major doubt after picking up an ankle injury against Fulham on Saturday, but will be ready for European action.
John O'Shea is another pushing for a starting berth after successfully shaking off a heel problem.
The Irishman is expected to slot in at right-back, with Ferdinand set to partner Nemanja Vidic in the centre of the back four.
Long-term absentees Gary Neville and Wes Brown remain sidelined, along with Rafael da Silva, but Ferguson has no fresh injury or suspension concerns to contend with.
Injury woesIn contrast, Mourinho has seen his defence decimated by injuries in the build up to the game.
Marco Materazzi, Nicolas Burdisso and Christian Chivu will all miss the crunch contest after picking up knocks in recent weeks.
Materazzi and Burdisso were forced out of Inter's 2-0 win over Genoa at the weekend, sustaining hamstring and thigh problems respectively.
Argentine centre-half Walter Samuel is also doubtful, with Mourinho unlikely to risk the former Real Madrid man.
With their foundations rocked, Inter will be hoping their attacking unit can fire on all cylinders, with Zlatan Ibrahimovic and Adriano expected to lead the line.