The Blues boast an impressive record against their London rivals at Stamford Bridge, but they head into the match on the back of a disappointing run of form and are in need of victory.
The two-week break has given defending champions Chelsea a chance to regroup following a hugely inconsistent start to 2018, which has seen them fail to win back-to-back matches in the Premier League.
Their title now relinquished, the Blues are left desperately fighting for a top-four spot in the league and requiring success in the FA Cup to salvage their season. Even that, though, may not be enough to save Antonio Conte's job in West London.
In fact, if reports are to be believed it is now just a matter of weeks until Conte is given his marching orders by demanding owner Roman Abramovich, who is said to have already lined up Luis Enrique to take over from next season.
Adding the FA Cup to last season's Premier League crown - won with a record number of wins, remember - would not be a bad way for the Italian to bow out, though there is no doubt that the Blues have been hugely underwhelming in the top flight throughout 2017-18.
Right from the opening game of the season, when going down 3-2 to Burnley, Chelsea have seemingly been just one bad result away from a crisis, and Conte's long goodbye now appears to be entering its final stages.
Winning just seven of 18 matches in 2018, two of those via extra time or penalties, has seen the Blues drop out of the top four and exit the Champions League, leaving them with a maximum of 10 games to save face.
Chelsea's big game record has also been disappointing, having failed to win any of their last four matches against the big six, including back-to-back defeats at the hands of Manchester United and Manchester City a month ago.
The manner of the loss at City was particularly hard to take for supporters, with the Blues almost settling for a one-goal defeat, and now Conte must quite simply send out his players to attack Tottenham and reignite his side's top-four hopes.
Recent form in Premier League: LLWLLW
Recent form (all competitions): DLLWLW
While Chelsea have struggled for momentum over the past few months, Tottenham have lost just two of their last 25 matches and are in a strong position heading into this match.
Mauricio Pochettino famously said earlier in the season that the FA Cup is well down his list of priorities, though following the Lilywhites' cruel Champions League exit, winning domestic silverware is now surely a priority.
Finishing in the top four is a prerequisite for any domestic success, though, and as things stand it is Tottenham who are the strong favourites to edge out Chelsea for that final Champions League berth.
Liverpool in third are only two points better off than Spurs after playing a game more, too, so victory at Stamford Bridge this weekend and all focus can turn to the huge FA Cup semi-final with Man United in a few weeks' time.
The manner of the 3-2 aggregate defeat to Juventus may have been tough to take for Spurs, having dominated much of the last-16 tie, but Pochettino will be delighted with the response shown by his players following that latest setback in their quest for some form of silverware.
Bournemouth put up a fight but were eventually brushed aside, while Swansea City offered up far less resistance in the FA Cup ahead of the international break - Spurs running out comfortable 3-0 winners in that match, without the services of injured striker Harry Kane.
Kane's absence has not really had too much of an impact on the Lilywhites at all, in fact, as they have netted seven goals in 125 minutes without their leading goalscorer, helped by the form of Son Heung-min in a false nine role up top.
Widespread praise aimed at Tottenham only counts for so much, though - Pochettino must now use the remaining weeks of the season to nail down a top-four spot and finally end that decade-long wait for a trophy. Nobody, not even Chelsea fans, could argue against that being a pretty decent all-round campaign.
Recent form in Premier League: WDWWWW
Recent form (all competitions): WWWLWW
Despite initial fears that Kane could miss the remainder of the season, quickly downgraded to around a six-week layoff, Pochettino hinted at his pre-match press conference that the Englishman could make an appearance this weekend.
Spurs otherwise have a clean bill of health, so there are also decisions to be made at centre-back and at full-back. Toby Alderweireld came through international duty unscathed and is pushing for a start, while Ben Davies and Kieran Trippier face competition from Danny Rose and Serge Aurier on either flank.
Willy Caballero is waiting in the wings for just a second league appearance of the season if required, and Conte insists that he has no problem throwing Gary Cahill into a likely back three if Christensen is deemed unfit to start.
Arguably Conte's biggest selection call comes up top, though, as Olivier Giroud and Alvaro Morata are battling it out for the central striker role. Despite the latter's underwhelming form over the past few months, he will feel refreshed after a two-week rest which could see him favoured.
Chelsea possible starting lineup:
Courtois; Azpilicueta, Christensen, Rudiger; Moses, Kante, Fabregas, Alonso; Willian, Morata, Hazard
Tottenham Hotspur possible starting lineup:
Lloris; Trippier, Sanchez, Vertonghen, Davies; Dier, Dembele; Lamela, Alli, Eriksen; Son
Head To Head
Chelsea have never lost a home game to Tottenham during the Premier League era, last tasting defeat in this fixture in February 1990 when Gary Lineker scored the winner for Spurs.
The Blues have won 18 and drawn nine during that run, most recently prevailing 2-1 in November 2016 to end their opponents' 12-game unbeaten run to begin last season.
Tottenham's 25 games at Stamford Bridge without winning in the Prem is the longest that one team has gone at a single ground without victory.
We say: Chelsea 1-1 Tottenham Hotspur
Chelsea may have edged out Crystal Palace in their last league outing, but they have not won back-to-back games in the Premier League since December. Tottenham, with that terrible record at Stamford Bridge, have won more points in Premier League London derbies this season than any other side - four wins, one draw, two defeats - and will see a point as a positive result here.