The Magpies make the trip to the Etihad Stadium having put together a six-match unbeaten streak in the top flight, a run which has ensured that Steve Bruce and his side will not face a relegation battle during the closing weeks.
While second-placed City remain with an eight-point cushion over Leicester City, Pep Guardiola's side have lost three of their last six matches in the Premier League.
Although each of those setbacks have come away from home, the Spaniard will naturally be concerned that his team are not living up to his high expectations on a regular basis.
Despite Liverpool having already been crowned champions, Guardiola will want that rectified over the coming weeks, especially with City looking to win the FA Cup and their first-ever Champions League.
Guardiola may point to the hectic schedule as a reason for their indifferent results, but a lack of a ruthless streak in the final third was to blame in the defeat to Southampton on Sunday evening.
With the game in midweek coming just 10 days after City outclassed Newcastle in the FA Cup, Bruce will hope that his players have learned lessons from that humbling at St James' Park.
Although City only prevailed by a 2-0 scoreline, the margin should have been far wider, and Bruce will inevitably have to consider a different strategy for the visit to Manchester.
Nevertheless, recording 12 points from six matches in the Premier League highlights that his squad are in good shape heading into one of their toughest fixtures of the campaign.
While the Magpies will have 10th spot in their sights, they are aware that a heavy defeat against City could result in them dropping down to 14th position.
Manchester City Premier League form: LWWLWL
Manchester City form (all competitions): WWLWWL
Newcastle United Premier League form: DWWDWD
Newcastle United form (all competitions): WWDLWD
Having began the game at St Mary's on the substitutes' bench, Kevin De Bruyne is likely to be recalled to the City side.
As it stands, Aguero is the only player who will miss out through injury.
Bruce could opt to make sweeping changes to his Newcastle team for this game, while also switching back to five at the back.
Manchester City possible starting lineup:
Ederson; Walker, Otamendi, Laporte, Mendy; De Bruyne, Rodri, Gundogan; Foden, Jesus, Sterling
Newcastle United possible starting lineup:
Dubravka; Yedlin, Fernandez, Lascelles, Schar, Rose; Ritchie, Bentaleb, Shelvey, Lazaro; Joelinton
We say: Manchester City 4-1 Newcastle United
Despite Newcastle's good form heading into this contest, there is every expectation that City will produce a positive response from their setback at the weekend. Although Newcastle are performing well enough in attack to get on the scoresheet, they could ship several goals at the other end.