The famous fixture will be staged behind closed doors at the Tottenham Hotspur Stadium for the first time owing to the coronavirus pandemic.
Arsenal enter the fixture in better form than their local rivals and are a point better off in the final Europa League qualifying spot.
Far sooner than many had predicted, Tottenham supporters already appear to be losing faith in head coach Jose Mourinho following a poor set of results.
Spurs have won back-to-back home matches, against West Ham United and Everton, but those are their only two victories in 11 matches stretching back to mid-February.
Against a side horribly out of form and fresh on the back of shipping five to Manchester United, Tottenham failed to register a single attempt on target.
Not only have the results been disappointing, with Spurs exiting two cup competitions in the space of a week before the lockdown, the performances have arguably been even worse.
Mourinho possesses an array of attacking talent, not least prolific striker Harry Kane, but getting the most out of those players is proving very tough.
One positive for Mourinho has been an increase in clean sheets - three in their last four games - and he has called on his side to find a balance between attack and defence.
That is the only way Tottenham are going to keep their Premier League season alive, with a top-five finish now out of the question and the Europa League the best they can aim for.
Bitter rivals Arsenal are in a similar position, having been made to pay the price for a slow start to action last month when losing their first two games back.
In truth, the Gunners' problems go a lot further back than that, but it was after the 2-1 loss at Brighton & Hove Albion that Mikel Arteta seemed to realise the size of the task that he has inherited.
The Spaniard has gained a reputation for being a good tactician and Arsenal have certainly showed real signs of recovery in the three weeks since that loss on the South Coast.
In fact, Arsenal had won three games in a row without conceding before being pegged back in a late 1-1 draw with Leicester City in their most recent outing.
Their upturn in form has seen them climb above Tottenham into eighth, which will be enough for a European spot assuming Manchester City's continental ban is upheld by CAS.
Not since October 2018 have Arsenal won three away league games in a row, however, while Tottenham are seeking three successive home league wins for the first time in 15 months.
With more than just bragging rights on the line this weekend, both teams will be desperate to prolong those respective runs.
Tottenham Hotspur's Premier League form: DDWLWD
Tottenham Hotspur's form (all competitions): LDWLWD
Arsenal's Premier League form: WLLWWD
Arsenal's form (all competitions): LWWWWD
Just when he was enjoying a run in the side in his favoured centre-back position, Eric Dier has been hit with a four-match ban by the FA for confronting a supporter after March's FA Cup defeat to Norwich City.
Fellow first-team regular Dele Alli is doubtful, meanwhile, having missed Tottenham's last two games with a minor hamstring problem.
Kane's place in the starting lineup is not in doubt as the Englishman looks to add to his tally of 10 goals against Arsenal, making him the fixture's outright top scorer.
Arsenal also have a player suspended for their short trip across town as Eddie Nketiah was sent off shortly after being brought on against Leicester.
Arteta has been rewarded with his decision to switch to three at the back and there is no reason why that will change on Sunday, possibly with the same XI from the Leicester draw.
Leading scorer Pierre-Emerick Aubameyang has been involved in four goals in his last three Premier League games against Spurs, but each of those came at the Emirates Stadium.
Tottenham Hotspur possible starting lineup:
Lloris; Aurier, Alderweireld, Vertonghen, Davies; Sissoko, Winks, Lo Celso; Lucas, Kane, Son
Arsenal possible starting lineup:
Martinez; Mustafi, Luiz, Kolasinac; Bellerin, Xhaka, Ceballos, Tierney; Saka, Lacazette, Aubameyang
Head To Head
Tottenham are unbeaten in their last five home league meetings with Arsenal, although this will be their first such meeting at the Tottenham Hotspur Stadium.
The Gunners have kept just one clean sheet in their last 10 top-flight trips to their closest neighbours, coming in a 1-0 victory six years ago.
In terms of this season's reverse fixture, Spurs squandered a two-goal lead eight months ago to draw 2-2.
Indeed, Tottenham have dropped 42 points from winning positions against Arsenal in the Premier League - more than any side has dropped against another in the competition's history.
We say: Tottenham Hotspur 1-1 Arsenal
Arsenal have been in good form over the past few weeks and have overtaken Tottenham in the table. The Gunners are winless in five league trips to Spurs, however, and we are tipping this first ever encounter between the sides at the Tottenham Hotspur Stadium to finish level.