Victory in the 174th Manchester derby would see United leapfrog the hosts and inflict further damage on Pep Guardiola's stuttering side.
It's already been a disappointing campaign for the Catalan, after their last chance of silverware ended with FA Cup defeat to Arsenal at the weekend.
That means that Guardiola faces the alien prospect of a season without a trophy for the first time in his illustrious career.
A failure to qualify for the Champions League is almost unthinkable and would make his first campaign in charge a complete write-off.
City come into the match a place and a point above us, so the victor at the Etihad will take pole position in the race for the top four.
As mentioned, we'd not only move about City with a win but also level on points with third-placed Liverpool.
We'll have to do so without world record signing Paul Pogba however, who will miss out with a muscle injury.
He joins Juan Mata, Chris Smalling, Phil Jones, Marcos Rojo and Zlatan Ibrahimovic on the sidelines, but Antonio Valencia and Ander Herrera are set to feature.
Gabriel Jesus, John Stones and Bacary Sagna are all doubtful for trophyless City, but key duo David Silva and Sergio Aguero are expected to be fit despite limping off on Sunday.
Honours are even between the two so far this season with one win apiece (2-1 City in the league, 1-0 United in the cup) ahead of this twice-rearranged Manchester meeting.
Originally scheduled to be played on the weekend of the EFL Cup final, the game was moved again to a rare Thursday night slot because of a television clash.
United boss Jose said:
"There is one between the teams so it is an important match and the situation is open.
"It is an objective to finish in the top four but we are a club that is made to fight for trophies.
"We don't have a chance of winning the Premier League but a 25% chance of winning the Europa League, so I think we have to put everything into it.
"Man City has to play Premier League football only but we have a semi-final in a European competition to play in, so it is a harder schedule for us.
"We will be giving our all in this big derby game because I know how much it means to the fans if we can win it."
Form guide: City D D L W W L United D W D W W W