For the first time since January 2017, Spurs go into a showdown with Man City sitting above their opponents in the table, and victory would lift them to the very top until at least Sunday night.
Matches with Mourinho and Guardiola in opposing dugouts almost demand that as much attention be focused on the managers as the clubs, and both will be looking to crown celebratory weeks here - Mourinho having passed his one-year anniversary as Spurs boss and Guardiola after finally putting pen to paper on a new two-year contract at the Etihad Stadium on Thursday.
Arguably the two highest-profile managers in football have faced off in Clasicos and Manchester derbies before, with Guardiola enjoying the better of their past meetings.
Indeed, Mourinho's 10 defeats to Guardiola-led teams are more than he has suffered against any other manager, while Guardiola himself has only beaten Manuel Pellegrini more often as an opposing boss.
The dynamics may be a little different heading into Saturday's showdown, though, with Tottenham flying high and belief beginning to grow that they could launch a genuine title challenge this season - just one year after finishing 40 points off the pace.
There is still a long way to go, of course, but the signs were promising before the international break, with Spurs embarking on the longest current unbeaten run in the league and picking up 17 points from the 21 on offer in that time.
Another victory this weekend would secure four league wins on the bounce for the first time since February 2019, while their only setback in their last 14 outings across all competitions came away to Antwerp in the Europa League last month.
If there is a concern for Spurs right now it may come in the fact that only two of their Premier League matches this season have been decided by more than one goal, and their last three have seen them only scrape past Burnley, Brighton & Hove Albion and West Bromwich Albion.
Mourinho's men have still picked up nine points from nine in those games, though, while they head into this weekend boasting the joint-best defensive record, the joint-best goal difference and the joint second-best attacking record in the division.
Even so, Mourinho may still be demanding an improvement from his side, whose relatively kind fixture list since the October international break has now well and truly ended.
Six of Tottenham's next seven league games come against teams that finished in the top eight last season - Man City, Chelsea, Arsenal, Liverpool, Leicester City and Wolverhampton Wanderers - while they must also play three Europa League games and an EFL Cup quarter-final in that spell.
Tottenham's true title credentials may be a lot clearer by Christmas, then, and by that stage Man City will hope to have hauled themselves back into the front-running of that conversation too.
Guardiola's side have only won three of their seven outings so far this season, dropping nine of the 21 points available to them to find themselves 10th in the table.
However, City do still boast a game in hand over most of the other teams in the league and are only six points off pace-setters Leicester, so they certainly have the scope to make up for their uncharacteristically sluggish start.
A 1-1 draw at home to champions Liverpool last time out was the third time they have shared the spoils in their last five Premier League games - as many as their previous 70 outings in the competition.
City's struggles to turn those draws into wins can be directly correlated to their relative lack of goals this season, having found the back of the net only 10 times in their seven league games.
To put that into context, City had plundered 27 goals by the same stage of last season, and their current tally is their lowest after seven games since 2010-11.
Guardiola's men have failed to score more than once in each of their last five Premier League games, having netted 16 times in their previous five before that.
It should be noted that City have not completely dried up in front of goal - their tally of nine goals in three Champions League games is bettered by only two other clubs, for example - but their Premier League profligacy will be a growing concern.
Guardiola may subsequently be hoping that his players carry their international form into domestic duties, having seen Ferran Torres score a hat-trick for Spain against Germany, Rodri also get on the scoresheet in that match and Ruben Dias net twice for Portugal against Croatia.
However it comes, Guardiola will know the importance of returning to winning ways this weekend, whereas victory for Spurs would be another statement of intent in what supporters increasingly hope could be a memorable campaign.
Tottenham Hotspur Premier League form: DWDWWW
Tottenham Hotspur form (all competitions): WWLWWW
Manchester City Premier League form: LDWDWD
Manchester City form (all competitions): WDWWWD
Ake is expected to miss this weekend's match despite his injury not being as serious as first feared, but Sterling could be in contention for the trip to North London as Mourinho mischievously suggested in his press conference.
City could also be boosted by the return of record scorer Sergio Aguero, who has struggled with a hamstring injury recently but used the international break to get back up to speed.
The Argentine has scored 11 Premier League goals against Spurs - his second-favourite opponent after Newcastle United - but 10 of those came in his first seven meetings, with only one goal in the subsequent nine.
If he is passed fit, Aguero may be eased back in as a sub, particularly with Gabriel Jesus now back fit and firing; he has been involved in 11 goals in his last 11 games in all competitions and could score in four consecutive Man City appearances for the first time since April 2018.
Benjamin Mendy and Fernandinho have also used the international break to gather fitness after recent injury problems, but this match will come too soon for either to be thrown straight into the starting lineup.
There is also uncertainty surrounding Oleksandr Zinchenko, who was part of the Ukraine squad placed into quarantine by Swiss authorities after a positive test ahead of their cancelled international meeting.
Spurs, meanwhile, will be without Matt Doherty after he tested positive for coronavirus while away with the Republic of Ireland.
Doherty came into close contact with clubmate Gareth Bale during a match between Ireland and Wales, but the Real Madrid loanee has not tested positive himself and so is available this weekend as things stand.
Steven Bergwijn was sent home from Netherlands duty after international doctors deemed him not fit enough to feature, but he will be in contention for this match.
Spurs will again look to Harry Kane for their main goal threat - he has been involved in 23 goals in just 14 games across all competitions this season, at least eight more than his closest Premier League rival, which happens to be teammate Son Heung-min.
Tottenham Hotspur possible starting lineup:
Lloris; Aurier, Alderweireld, Dier, Reguilon; Sissoko, Hojbjerg; Bale, Lo Celso, Son; Kane
Manchester City possible starting lineup:
Ederson; Walker, Dias, Laporte, Cancelo; De Bruyne, Rodri, Gundogan; Torres, Jesus, Sterling
Head To Head
Spurs remained unbeaten against Man City last season, including a 2-0 win in the corresponding fixture which ended a run of six top-flight meetings without a victory.
Indeed, Tottenham have now won both of their home games against Man City at the Tottenham Hotspur Stadium and could triumph in three consecutive home editions of this fixture for the first time since a run of six between 2005 and 2009.
Spurs have beaten Man City 24 times in total during the Premier League era, a tally of victories only Chelsea can better against the Citizens.
We say: Tottenham Hotspur 2-2 Manchester City
We could learn a lot about Tottenham's title credentials from this match. Victory would be a real statement of intent, and Man City's patchy form this season will make them confident of pulling off a win that would send them to the summit.
However, Man City's failure to score more than once in a Premier League game can surely not go on for much longer, and we expect them to come away from this match with a point.
Top betting tip
Watch the Sports Mole Football Shorts prediction for this game below:
Our analysis of all available data, including recent performances and player stats up until an hour before kickoff, suggested the most likely outcome of this match was a Manchester City win with a probability of 56.07%. A draw had a probability of 22.5% and a win for Tottenham Hotspur had a probability of 21.44%.
The most likely scoreline for a Manchester City win was 1-2 with a probability of 9.89%. The next most likely scorelines for that outcome were 0-1 (9.88%) and 0-2 (9.24%). The likeliest drawn scoreline was 1-1 (10.57%), while for a Tottenham Hotspur win it was 2-1 (5.66%). The actual scoreline of 2-0 was predicted with a 3% likelihood.