The Red Devils have lost just one of their last 12 outings across all competitions, including a 1-0 win over Watford in the third round of this competition at the beginning of the month.
In that time United have also moved to the top of the Premier League table, now six points clear of champions Liverpool, whose only win and only goals so far this calendar year have come in the FA Cup.
Here, Sports Mole looks at how Ole Gunnar Solskjaer could line his side up for the fourth-round showdown.
Solskjaer must decide which balance to strike with his side facing difficult opposition this weekend but his priority also being the title race, which has unexpectedly unfolded in front of his side.
Marcus Rashford is almost certain to return to the starting lineup after being rested against Fulham in midweek, but Solskjaer could otherwise keep faith with key players such as Bruno Fernandes, Harry Maguire and Paul Pogba, despite the temptation to rest them.
Pogba in particular has rediscovered his best form in recent weeks, scoring another wonder goal to see United past Fulham, and he could again be deployed in a wide forward role as he was at Anfield a week ago.
Edinson Cavani will be hopeful of keeping his place up front ahead of Anthony Martial, but there are likely to be other changes elsewhere with fringe players such as Alex Telles, Dean Henderson and Nemanja Matic coming back in.
Scott McTominay scored the only goal of the third-round win over Watford and so should come back into the midfield for this one, while Victor Lindelof is expected to overcome the back issue which saw him sit out of the Fulham game in time to start again this weekend.
Brandon Williams, Marcos Rojo and Phil Jones all still remain sidelined, though, while summer signing Facundo Pellistri is again set to be forced to wait for his debut.
Solskjaer could include January arrival Amad Diallo in his matchday squad, though, with the winger in contention to make his debut this weekend.