Spurs have gone 12 matches unbeaten under the arch, where they are based this term while the club's new stadium is completed.
But Arsenal have reason for optimism after new signings Pierre-Emerick Aubameyang and Henrikh Mkhitaryan put in an encouraging display against Everton last week, and the Gunners themselves boast a good record at the national stadium.
Indeed, Arsene Wenger's men have emerged victorious on each of their last nine visits to Wembley.
Who will come out on top? James Olley assesses the key talking points ahead of the north London derby...
Can Arsenal beat the press?
The Gunners’ defending has been a cause for concern this season, particularly when teams press the ball high up the pitch as Tottenham are likely to attempt at Wembley. Arsenal have been guilty of gifting possession to their opponents in vulnerable areas in a series of damaging defeats on the road — something Mauricio Pochettino’s team will look to exploit. Granit Xhaka has been guilty on occasions of failing to track runners in those circumstances – Swansea’s equaliser in last week’s defeat at the Liberty Stadium being the latest example — and the midfielder must use the ball intelligently while protecting his defence.
Will new boys pick up where they left off?
There were plenty of encouraging signs in last Saturday’s 5-1 defeat of Everton that Arsenal can reap the benefits of the understanding between Pierre-Emerick Aubameyang and Henrikh Mkhitaryan, who both joined the club last month. The pair were hugely effective during three seasons together at Borussia Dortmund up to 2016 and Mkhitaryan set up Aubameyang’s goal on his Gunners debut. Eric Dier and Mousa Dembele are likely to be charged with stopping the supply line for Tottenham, although Mkhitaryan’s movement will make that difficult as he regularly interchanges positions with Alex Iwobi and Mesut Ozil in behind Aubameyang.
Will Tottenham’s full-backs do the damage?
Pochettino has regularly rotated his full-backs, with Tottenham reliant on the width they bring to open teams up at Wembley. Arsenal are unlikely to defend deep for long periods but Kieran Trippier and Ben Davies, if selected, will still be required to overload their opponents in wide areas, taking advantage of any lapses of concentration from the Gunners’ midfielders. Nacho Monreal will give Spurs something to think about going the other way given he has two goals in his last four games and has thrived since Arsene Wenger reshuffled Arsenal into a four-man defence.
Can Kane continue to thwart Arsenal?
He played for Arsenal as a schoolboy but Harry Kane saves some of his most ruthless form for Tottenham’s north London rivals. Kane has scored six goals in as many Premier League games against Arsenal, only failing to score in one of those. He has four in three at home in the League and his record against London sides, like many of his statistics, is bordering on the absurd: Kane has netted 21 goals in 32 London derbies in the League to date at a rate (0.66 per game) only bettered by Gunners legend Thierry Henry (0.73).