The Hammers are currently fighting relegation but will be buoyed by their FA Cup victory at home against Brentford on Monday night.
West Ham defeated the Bees 5-3 on penalties after a thrilling and entertaining 2-2 draw to progress to the quarter finals of the cup.
The Hammers currently sit 18th in the league but a win can lift them out of the relegation zone.
The Irons are now hoping to repeat their performance against title contenders Man City, but Santo warned his players that it won’t be easy.
Speaking at his weekly pre-match press conference Santo Said: “They have a lot of options and have many talented players who can play in different position. They have an identity of a way they play football. Any player they put inside they put inside they click immediately.”
Santo also said he felt sympathy for Tottenham goalkeeper Antonin Kinsky after he was replaced in the 17th minute of their Champions League last-16 tie at Atletico Madrid after conceding three goals. His first error - a slip - led to Marcos Llorente making it 1-0 in the sixth minute.
He said: “This is football. It happens. But I hope he bounces back. Being a goalkeeper can be very stressful. There is no hiding place for goalkeepers. You are responsible. It can be stressful but different stress to others roles.”
West Ham United are winless in 20 Premier League matches against Manchester City (D3 L17), since a 2-1 win in September 2015. It’s their longest ever winless league run against an opponent.
West Ham have never beaten Manchester City at the London Stadium in the Premier League in nine attempts (D2 L7) – they have only faced Brighton as often without winning there (D7 L2).
Following a 1-0 win over Fulham last time out, West Ham are looking to win consecutive Premier League games for the third time this season, previously doing so in November (v Newcastle and Burnley) and January (v Spurs and Sunderland).