The Citizens have won just three of their seven league outings so far this season, but could still temporarily move to within three points of leaders Leicester City with a game in hand should they beat Spurs.
However, Jose Mourinho's side are one of the division's form teams heading into the latest showdown between arguably the two highest-profile managers in world football.
Here, Sports Mole looks at how Guardiola could line his side up for the contest.
Man City could be missing some key players for the trip to North London, perhaps most notably Raheem Sterling after he picked up a calf injury during training with England while away on international duty.
The winger was sent home ahead of Wednesday's win over Iceland but has since been back in training with his club and so could feature this weekend, with Mourinho mischievously predicting that the winger was certain to start despite his international absence.
Any absence for Sterling could open the door for Phil Foden to return to the starting lineup, and the youngster's two-goal showing for England in that win over Iceland would have done his chances no harm at all.
Sergio Aguero could be back available after a hamstring injury as he looks to improve on a record of one goal in his last nine meetings with Spurs - having scored 10 in his first seven - but he is unlikely to be thrown straight into the starting XI with Gabriel Jesus now back fit and firing.
The Brazilian has been directly involved in 11 goals in his last 11 appearances, including scoring in each of his last three Man City outings. Another goal this weekend would see him net in four games on the bounce for the first time since April 2018.
Indeed, it was a productive break for Man City players in front of goal with Ruben Dias even scoring twice for Portugal against Croatia, although Guardiola will have no doubt cursed the schedule once again when Nathan Ake limped off with a hamstring injury early on in Netherlands' match against Spain.
Ake is expected to miss this game as a result but may not be set for a prolonged spell on the sidelines, while Oleksandr Zinchenko's situation remains unclear after the Ukraine squad was quarantined in Switzerland following three positive tests within their party.
Fernandinho and Benjamin Mendy were both pencilled in for returns after the international break and will be assessed ahead of this match.
Watch the Sports Mole Football Shorts prediction for this game below: