With City realistically out of the Premier League title race, Guardiola has placed extra priority on successfully defending the trophies which were won in the domestic cups last season.
While the club have coasted through to the last 16 of the FA Cup courtesy of home wins over Port Vale and Fulham, a two-legged tie with United in the semi-final of this competition instantly raised the stakes.
United would have fancied their chances of establishing a lead ahead of the second leg at the Etihad Stadium, especially having overcome their neighbours just a month earlier.
However, City were outstanding during the first half at Old Trafford, and they squandered opportunities to be further than three goals ahead at half time.
There would have been disappointment over letting United back into the tie during the second half, although Guardiola and his squad will feel that they already have one foot in February's final.
Aware of the importance of getting one over their struggling rivals, Guardiola rested Kevin De Bruyne at the weekend, a move he would have felt was necessary with the Belgian having already started five times since the turn of the year.
During those outings, De Bruyne has contributed just three assists, but the presence of the 28-year-old will be enough to put United on the defensive during the opening stages of this game.
Sergio Aguero also missed out against the Cottagers, meaning that the Argentine will likely be provided with the chance to build on his seven goals from four games during 2020.
Regardless of their expected recalls, Ole Gunnar Solskjaer will already acknowledge that his United team are up against it on Wednesday, despite Sunday's demolition of Tranmere Rovers.
While netting six goals against the League One outfit can only improve the belief within the squad, more negative chants from the stands accompanied their progress into the FA Cup fifth round.
Despite the Glazer family and Ed Woodward bearing the brunt of the hostile signing, Solskjaer knows that he has a responsibility to deliver an improved run of form on the pitch.
The Norwegian will hope that his ambitions are matched with at least one fresh face before the end of the January transfer window, although that appears far from a certainty ahead of Friday's deadline.
For now, Solskjaer must rely on the same group of players which succumbed so tamely in the first leg, as well as against Burnley in the Premier League last week.
There is an argument that United's style of play is arguably more suited to playing away from home, as shown when they outperformed City in December.
That said, Marcus Rashford - now sidelined until at least April - played a significant part in that success, and Solskjaer is under pressure to find a solution in the coming weeks and months.
Whether or not that materialises against City, United fans want to see signs of forward steps being made, rather than having to witness what feels like stagnation both on and off the pitch.
Manchester City EFL Cup form: WWWW
Manchester City form (all competitions): WWWDWW
Manchester United EFL Cup form: DWWL
Manchester United form (all competitions): LWWLLW
Having picked up knocks at the weekend, Joao Cancelo and Mahrez will be assessed before Guardiola finalises his squad.
United boss Solskjaer has less room to manoeuvre, with Paul Pogba and Rashford among six players who remain on the sidelines.
Manchester City possible starting lineup:
Ederson; Walker, Stones, Fernandinho, Mendy, De Bruyne, Rodri, Gundogan; Bernardo, Aguero, Sterling
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Lindelof, Maguire, Williams; Fred, Matic; Greenwood, Mata, James; Martial
Head To Head
Wednesday's showdown will represent the 181st competitive meeting between the two clubs, with United recording 74 wins in comparison to 54 victories for City.
Despite the contrasting trajectories of the two clubs, City have not necessarily dominated this head-to-head in recent years, prevailing just five times in nine attempts.
United have avoided defeat on three of their last four visits to the Etihad, which includes a 2-1 triumph as recently as December 7.
We say: Manchester City 3-1 Manchester United
While United should put up more of a fight than they did two weeks ago, we still expect City to canter through to the final. United will likely have to find an early goal to impose themselves on opponents who would have learned from their defeat in the same fixture last month.
body check tags ::