Ole Gunnar Solskjaer's side are looking to dethrone the champions, who have lifted the trophy in four of the last six seasons including both of the last two.
What looked on paper like a difficult January has proven to be exactly that for Manchester United so far, with the Red Devils still looking for their first win and first goal of the New Year.
Things do not get any easier with the visit of Man City either, although it was against Pep Guardiola's side that United produced arguably their best performance of the season to date.
Tuesday will mark exactly one month since that 2-1 triumph at the Etihad Stadium, and it has been a month as tumultuous as their entire campaign so far.
The frustration for United fans has been their inconsistency, with a tendency to suffer a hugely disappointing setback just when it looks as though they have turned a corner.
That affliction has not yet cost them in this competition, although their route to the EFL Cup semi-finals has not been entirely straightforward.
Rashford was on the scoresheet again during a 3-0 victory over Colchester United in the last round, although this derby is sure to be their toughest test yet as they chase a sixth League Cup crown.
That would see them draw level with Man City's tally, four of which have come in the last six seasons as the club has dominated this competition.
Guardiola's side are bidding to become the first team since Liverpool from 1981 to 1984 to lift the trophy three years in a row, and with the Premier League now surely out of reach every other piece of silverware takes on that extra level of importance.
City safely secured their place in the fourth round of the FA Cup on Sunday courtesy of a 4-1 win over Port Vale, making it three wins in a row across all competitions since their costly defeat to Wolves.
The result continued a relatively routine passage through the cup competitions so far this season, with City having scored three times in each of their EFL Cup games this term.
Preston North End, Southampton and Oxford United have all been beaten en route to the semi-finals, taking Man City's winning run in the competition up to 15 games stretching back to October 2016.
Indeed, United were the last team to inflict an EFL Cup defeat on Man City, and they went on to lift the trophy themselves that season too.
Should they do the same again then they will fancy their chances of beating either Leicester City or Aston Villa in the final, although with the second leg at the Etihad Stadium to come later this month they will know that building a substantial lead in this first leg could prove vital.
Man City always take this competition very seriously, though, and are justifiably the bookmakers' favourites to claim the trophy yet again.
Man Utd EFL Cup form: WWW
Man Utd form (all competitions): WLWWLD
Man City EFL Cup form: WWW
Man City form (all competitions): WWLWWW
Sergio Romero is likely to keep his place in goal, while other fringe players could also get another chance after the FA Cup outings at the weekend.
The likes of Fred and Rashford will be hopeful of coming back into the side, though, with Solskjaer likely to field a slightly stronger team than the one which drew with Wolves.
Man Utd possible starting lineup:
Romero; Wan-Bissaka, Lindelof, Jones, Williams; Fred, Matic; Greenwood, Lingard, Rashford; Martial
Man City possible starting lineup:
Bravo; Cancelo, Garcia, Fernandinho, Zinchenko; Foden, Rodri, De Bruyne; Bernardo, Jesus, Sterling
Head To Head
Fixtures between these two sides have been more even than their overall fortunes suggest they should have been in recent years, with five wins apiece from the last 12 meetings.
United have not won back-to-back derbies since 2010, although on that occasion the first of those did come in a League Cup semi-final.
There have been seven League Cup meetings between these two sides before, and the honours are evenly matched at three wins apiece with one draw.
We say: Man Utd 1-1 Man City
First legs of semi-finals can often be tense affairs, and this one is unlikely to be different, particularly with the added pressure of it being a derby. We can see the two sides cancelling each other out, which would give Man City the slight advantage heading into the second leg.