The Blues beat United 1-0 at Wembley Stadium in May's showpiece to lift the famous trophy for an eighth time, but both sides are now under new management and it is the Red Devils who are in the better overall form.
Chelsea may be on the brink of sealing a place in the last 16 of the Europa League, into the last eight of the FA Cup and a week away from facing Manchester City in the final of the EFL Cup, but Maurizio Sarri remains under intense pressure at Stamford Bridge.
The Blues have lost their last three Premier League away games by a combined 12 goals, following up a 2-0 loss at Arsenal and a 4-0 reverse at Bournemouth with a crushing 6-0 defeat against Man City - their heaviest defeat since going down 7-0 at Nottingham Forest in April 1991.
Sarri's men did at least respond with a 2-1 victory in the first leg of their Europa League last-32 tie at Malmo in midweek, with the Italian boss fielding a mixed XI for that match, knowing that any sort of loss in Sweden may well have signalled the end of his time in West London.
As it is, Sarri will now surely remain in charge for at least the next three matches, with all focus on the cup competitions. A big week for Chelsea starts with the visit of Man United in the FA Cup and ends with that EFL Cup final showdown with Man City, sandwiching the visit of Malmo in the Europa League.
Three wins from three will be the target for Sarri, who admitted earlier this week that he has not had any sort of contact with absent owner Roman Abramovich, despite a disappointing run that has seen the Blues go nearly two months since last winning back-to-back league matches.
The immediate priority is progression in the FA Cup, of course, and Chelsea are looking to reach the quarter-finals for the fourth consecutive season, reaching the final in each of the last two. Following defeat to Arsenal in the 2017 final, Chelsea responded well by beating United through an Eden Hazard penalty 12 months on.
That was not enough to save Antonio Conte, though, with Chelsea chiefs swinging the axe a little over a month later and bringing in Sarri. Famed for his passing style at Napoli, the 60-year-old has yet to get his players to adapt to his ways and, if certain reports are to be believed, time is ticking down for him to get things right.
Chelsea really are specialists when it comes to the FA Cup, going nine games without defeat since the 2017 final, and losing just that one match in their last 15. A word of warning for the Blues, though - Monday's opponents have eliminated the holders 10 times, more than any other side in the competition's history, last doing so in 2011-12 against Man City.
Recent form in FA Cup: WW
Recent form (all competitions): WWLWLW
Solskjaer did suffer his first real setback on Tuesday evening, though, as his side crashed to a 2-0 home loss at the hands of Paris Saint-Germain, surely all but ending their hopes of progression in the Champions League.
As the iconic United striker said himself, however, the Red Devils now have a chance to prove exactly what they are made of by responding in the best manner possible on Monday. After winning 10 and drawing one of their previous 11 matches, there can be no denying that the feel-good factor is back at Old Trafford.
Exiting the FA Cup really would be a massive blow for Solskjaer, who would happily take on the job full-time if offered to him, but he can at least fall back on United's incredible rise up the Premier League table.
From 11 points adrift of Chelsea when losing 3-1 to Liverpool in Mourinho's final game on December 16, the Premier League's most successful side are now a point better off than their opponents in fourth place. That, more than any domestic cup, will surely persuade United officials to give the job to Solskjaer.
Going all the way in the FA Cup will only strengthen calls for the fan favourite to stay on beyond the summer, and Solskjaer certainly boasts plenty of pedigree in this competition as he won it a couple of times as a player. Since helping his side to lift the trophy in 2004, however, United have gone all the way only once.
United have made it to the quarter-finals in each of the last four campaigns - not since between 1962 and 1966 have they reached the last eight five years in a row - but they have all too often fallen just short, something that Solskjaer will be looking to put right.
The Red Devils have already knocked out Arsenal en route to this stage, producing a superb display to win 3-1 at the Emirates Stadium last month. In a wide open last eight, Solskjaer's men will fancy their chances of adding some more silverware to their cabinet if they can overcome another of their heavyweight rivals.
Recent form in FA Cup: WW
Recent form (all competitions): WWDWWL
Man United will be without Jesse Lingard and Anthony Martial for this trip to Stamford Bridge as both players limped off in the midweek loss to PSG. Lingard injury his hamstring and Martial tweaked his groin, ruling both men out for the next few weeks.
Alexis Sanchez failed to make any sort of impact when replacing Martial on the left of United's front three, and the Chilean is also believed to have picked up a knock to leave him doubtful for this tie.
Juan Mata and Romelu Lukaku, two other subs against PSG, could therefore be handed a route back into the side, while Marcus Rashford should continue leading the line after scoring six goals in his last 10 matches.
Solskjaer has revealed that youngsters Tahith Chong and Angel Gomes may be part of his squad, but neither is likely to start in West London given the magnitude of the match and the full week's rest between matches.
Elsewhere, Antonio Valencia and Matteo Darmian are still nursing injuries and Marcos Rojo is a long-term absentee, but Chris Smalling and Phil Jones will be pushing for recalls in the heart of defence.
In terms of the home side, Sarri is expected to recall Hazard and Gonzalo Higuain after naming the attacking pair among his subs for Thursday's win at Malmo.
Higuain's likely recall will spell bad news for Olivier Giroud, who has had a hand in 23 goals in 28 appearances in the FA Cup, averaging a goal or assist every 73 minutes in the competition, though he could play a pivotal role from the bench.
Despite questions being asked for Sarri's formation, the under-fire Italian will almost certainly retain faith in Jorginho as the central pivot of his three-man midfield, alongside N'Golo Kante, with one of Ross Barkley, Ruben Loftus-Cheek or Mateo Kovacic completing the trident.
Loftus-Cheek sat out the midweek trip to Sweden with a back problem, however, and centre-back Gary Cahill is another who is nursing an injury.
Chelsea possible starting lineup:
Kepa; Azpilicueta, Rudiger, Luiz, Emerson; Kante, Jorginho, Barkley; Willian, Higuain, Hazard
Manchester United possible starting lineup:
Romero; Young, Jones, Smalling, Shaw; Herrera, Matic, Pogba; Mata; Lukaku, Rashford
Head To Head
This will be the 14th time that these two sides have met in the FA Cup. Chelsea have triumphed in each of the last four and could become the first side to win five successive ties against United.
The Red Devils have lost three of their last five FA Cup matches against Chelsea at Stamford Bridge, with those wins coming in back-to-back campaigns in 1998 and 1999.
In all competitions, United have won just two of their last 22 away games against the Blues, failing to win any of their last nine, including a 2-2 draw three months ago when Barkley scored in the final seconds of the match.
We say: Chelsea 2-1 Manchester United
Man United are out for revenge after losing last season's final and they are the side in better form, even accounting for their midweek wobble when losing to PSG. Chelsea have looked better at home than away, however, winning five in a row at Stamford Bridge and thumping an admittedly poor Huddersfield Town 5-0 last time out, and they will be keen to send out a message on Monday.