Not since 1990 have the Lilywhites returned from the home of their London rivals with all three points, suffering 18 defeats and drawing nine times during that run.
Spurs know that anything less than defeat on Sunday afternoon will leave them as strong favourites to hold down a spot in the top four, though, having built up a five-point gap on their fifth-placed opponents.
Here, Sports Mole looks at how Mauricio Pochettino could set out his team for the huge showdown.
Tottenham have a near clean bill of health heading into the match, with the obvious exception being the expected loss of Kane to an ankle injury. Pochettino sprang a surprise of sorts by revealing at his pre-match press conference that the Englishman could yet feature against Chelsea, though, just three weeks after picking up what some feared was a season-ending injury.
Son Heung-min still appears almost certain to get the nod to start in West London, though, having enjoyed a run of seven goals and an assist in his side's last five outings.
Pochettino is unlikely to change things too much on the back of the 4-1 win at Bournemouth in Tottenham's most recent league outing, the expected absence of Kane aside, and may therefore stick with Christian Eriksen and Dele Alli in attacking midfield, joined by one of Erik Lamela or Lucas Moura.
Elsewhere, Pochettino also has a big call to make following Toby Alderweireld's return to fitness - does he continue to go with Jan Vertonghen and Davinson Sanchez or restore the centre-back partnership that has worked so well in recent years?