Coming off their rollercoaster 5-4 defeat to Everton in the FA Cup on Wednesday, Spurs are looking to bounce back by completing a league double over Manchester City for the first time since 2015/16.
After making a goalscoring return from injury against West Bromwich Albion last Sunday, Kane came off the bench and entered the fray at Goodison Park early in the second half and played a pivotal part over an eventual 67 minutes, scoring Spurs' equaliser to take the tie to extra time.
As we'll get into, Kane has caused the Citizens issues in years gone by and will be hoping to do so again to kickstart Spurs' second half of the season.
Due to injuries, Kane has only faced City 11 times over his career - 10 times with Tottenham and once with Norwich City while on loan.
The Lilywhites striker boasts five wins, five losses and one draw, giving him a victory rate of around 44%.
Kane has netted two goals and laid on three assists in those outings, which have usually been full of entertainment.
The England captain most recently clashed with Guardiola's four-time title winning club in November, earning one of those assists - more on that later.
Looking to make his mark at the Etihad again, let's take a look at some of his best previous displays for Spurs.
Top five performances
Tottenham Hotspur 4-1 Manchester City
September 26, 2015
Coming off the back of a campaign which made him a household name, Kane was looking to follow up his 21-goal 2014/15 term and quash the 'one-season wonder' claims in this autumn clash.
Mauricio Pochettino's Lilywhites smashed Manuel Pellegrini's men, as the to-be White Hart Lane favourite earned a 8.7 rating on whoscored.com and opened his account with a second half strike.
His goal was far from spectacular, standing in an offside position before finishing a rebound from a Christian Erkisen free-kick but did manage four other shots and a joint game high three dribbles to boot.
Spurs would go on to finish third, one place above the Citizens in the top-flight table that season, despite being shock champions Leicester City's closest challengers for much of the campaign.
Manchester City 1-2 Tottenham Hotspur
February 14, 2016
Later that campaign, Kane and co recorded an equally impressive victory in Manchester as the striker scored from the spot to open the scoring.
Poch and Pellegrini met again at the Etihad as the Argentine completed a league double over the Chilean, who left that summer.
After City's own academy star Kelechi Iheanacho equalised in the second half, Eriksen finished a slick Spurs move to win it in the 83rd minute and prick a few ears heading into the run-in.
With a 78% pass accuracy, Kane's hold up play was key in the enthralling affair with no love lost on Valentine's Day.
Tottenham Hotspur 2-0 Manchester City
November 21, 2020
At 27 years old, the man who Mourinho said he could help 'explode' is in the prime years of his career and playing a new ball game under his Portuguese boss, best displayed in this contest earlier this term.
Often simply among the goals and not involved in general play under Pochettino, the arrival of the 'Special One' in November 2019 prompted a change of role for Kane.
The shift in style was on show in November as the skipper played a star grafting, defensive role in this titanic tussle of two early title chasers, setting up Giovani Lo Celso's second half strike to double Tottenham's lead.
Kane this time racked up an 80% pass success rate and made three tackles to earn the Lilywhites three important points prior to their winter struggles.
Tottenham Hotspur 1-3 Manchester City
April 14, 2018
Despite being defeated in this end of the season encounter, Kane put in a good personal performance against Pep's players at Wembley.
Gabriel Jesus and Ilkay Gundogan put the Mancunian side 0-2 up after 25 minutes before the soon to be World Cup Golden Boot winner set up Eriksen to score a first half consolation.
Winning three aerial duels and averaging a pass accuracy of 78%, Kane could at least hold his own head high in this capital contest.
Spurs once again finished third in Pochettino's penultimate term, as the Citizens became the first team in English top-tier history to reach 100 points.
Manchester City 2-2 Tottenham Hotspur
January 21, 2017
As both these sides aimed for title glory midway through the 2016/17 season, the points were shared, as Kane's assist helped his side complete a commendable comeback.
From being 2-0 down in the 54th minute, Dele Alli and Heung-min Son scored to earn a draw for Tottenham's travelling fans to enjoy, and Kane's delightful flick was one of many times that he and the South Korean have combined to help the Lilywhites hit the back of the net over the years.
Although he won just one aerial duel, failed to record a shot and only boasted a 53% pass accuracy, his penalty area awareness was imperative to Spurs' relatively successful result.
The 2016/17 campaign was Tottenham's best Premier League finish to date, second nine points behind winners Chelsea and eight ahead of the Citizens in third, who would go on to earn the crown across the next two campaigns.
Tip of the fixture
Kane is priced at 12/5 to score anytime on paddypower.com, with another 2-0 win to his side an outside shot at 45/1.
(Odds correct at time of writing, subject to change.)