Both sides got off to a strong start in the 2019-20 season and will be wanting to keep the momentum flowing.
It's expected to be a fierce battle between two quality tactical sides.
Here we present the complete match preview.
Team news and selection
City mid-fielder Fernandinho could play his first game since Copa America.
Star forward Sergio Aguero is also in contention for a recall to the starting XI.
Left-back Benjamin Mendy is continuing his rehabilitation after knee surgery, and Leroy Sane is a long-term absentee.
Dele Alli and Ryan Sessegnon are absent for Spurs.
Son Heung-min and Juan Foyth will miss the game due to suspension.
View from the managers ahead of the mega clash
"Since I came here to England, Spurs have been a real contender every season. In the first season, they finished second... they've always been there. They're the second-best team in Europe," said City manager Pep Guardiola.
"It is not a competition between him (Pep) and myself. Of course, I try to beat all the managers I'm going to face," said Spurs boss Pochettino.
City enter the game as favorites to win
Community Shield winners Man City had a clean sweep in England's top tier football last season by claiming all four trophies.
This season, the club has already got off the mark and had a breezy show in the EPL opener.
Man City's depth and quality all over could make life difficult for Spurs.
The attacking quartet, in particular, will trouble Spurs' backline.
Stat attack: Man City vs Spurs
Man City will be aiming to notch their fifth consecutive victory against Spurs in the Premier League. Spurs have managed to collect only four points from their last nine visits to the Etihad.
Dream11: Sterling, Kane lead this powerful line-up
Ederson gets the nod as the keeper of this Dream11 team
The four-man defense sees Toby Alderweireld, Aymeric Laporte, Davinson Sanchez and Oleksandr Zinchenko.
A utility mid-field is on offer. Moussa Sissoko forms the heart of the department and will be supported by David Silva and Kevin de Bruyne.
The match is set to start at 10:00 PM IST. It's scheduled to be held at the Etihad in Manchester. One can watch the match live on the Star Sports Network and stream the same on Hotstar (paid subscription). We expect City to win.