Victory for Pep Guardiola's side will see them crowned Premier League champions after being head and shoulders above the rest of the league this term.
They will have one eye on Tuesday's Champions League quarter-final second leg tie with Liverpool, but Guardiola will insist they remain focused for the clash with their bitter rivals.
Sky Bet: Manchester City v Manchester United odds: Including Raheem Sterling and Romelu Lukaku both to score, price boosted to 11/1
Man United, meanwhile, are still vying for second spot, with Liverpool hot on their heels, after a mixed season under Jose Mourinho.
The Red Devils have been criticised by fans and pundits this term, with performances and their style of play under the Portuguese being questioned after the amount of money they have spent.
They broke the transfer record (now held by Neymar) in 2016 to sign Paul Pogba from Juventus for £89m, along many more multi-million acquisitions across defence, midfield and their strike force.
So how does it compare with City, who spent £57m on Aymeric Laporte in January after another costly summer?
With figures compiled by the CIES Football Observatory, reported by the Daily Mail, the top most expensively assembled squads can be seen below...
Most expensive squads in world football
1. Manchester City - £777m
2. Paris Saint-Germain - £713m
3. Manchester United - £661m
4. Barcelona - £641m
5. Chelsea - £524m
6. Real Madrid - £439m
7. Liverpool - £408m
8. Juventus - £396m
9. Arsenal - £356m
10. Everton - £323m
