Spurs have been handed a tough group that also contains defending champions Real Madrid and may find themselves playing catch-up if they do not begin with a home win.
They will take on Peter Bosz's men without Dele Alli, though the former Ajax coach has a number of absences of his own to contend with.
|Game||Tottenham vs Borussia Dortmund|
|Date||Wednesday, September 13|
|Time||19:45 BST / 14:45 ET|
TV CHANNEL & LIVE STREAM
In the UK, the match will be available to watch live on television on BT Sport 3 and by stream via the BT Sport app.
|UK TV channel||Online stream|
|BT Sport 3||BT Sport app|
In the US, the match will be available to watch live on television on FS1 and by stream via Fox Sports Go.
|US TV channel||Online stream|
|FS1||Fox Sports Go|
SQUADS & TEAM NEWS
|Goalkeepers||Lloris, Vorm, Gazzaniga, Whiteman|
|Defenders||Trippier, Alderweireld, Vertonghen, Sanchez, Foyth, Aurier, Davies, Walker-Peters|
|Midfielders||Dier, Sissoko, Dembele, Eriksen, Winks, Georgiou, Oakley-Boothe|
|Forwards||Son, Kane, Llorente|
Tottenham are without Dele Alli, who was sent off in their final Europa League match last season and as a result starts a three-game ban.
The injured Victor Wanyama, Danny Rose, Georges-Kevin Nkoudou and Erik Lamela also miss out, but Mousa Dembele is expected to be available.
Potential starting XI: Lloris; Sanchez, Alderweireld, Vertonghen; Aurier, Dier, Dembele, Davies; Eriksen, Kane, Son.
|Position||Borussia Dortmund players|
|Goalkeepers||Weidenfeller, Reimann, Burki|
|Defenders||Zagadou, Subotic, Toljan, Beste, Sokratis, Piszczek, Toprak, Schumacher|
|Midfielders||Sahin, Dahoud, Pulisic, Kagawa, Castro, Bruun Larsen, Sauerland|
|Forwards||Yarmolenko, Gotze, Isak, Aubameyang, Philipp, Serra|
Dortmund have a lengthy injury list to contend with. They are particularly short at full-back due to the absences of Erik Durm, Raphael Guerreiro and Marcel Schmezler as well as Marc Bartra.
Sebastian Rode, Marco Reus and Andre Schurrle are also out but Julian Weigl has travelled and Neven Subotic could join the squad in London late if he recovers from illness.
Potential starting XI: Burki; Piszczek, Sokratis, Toprak, Zagadou; Castro, Sahin, Gotze; Pulisic, Aubameyang, Philipp.
BETTING & MATCH ODDS
Tottenham are 13/10 favourites to win, according to dabblebet, with Dortmund priced at 2/1 and the draw also available at 12/5.
Harry Kane is considered an 11/4 bet to open the scoring, while Pierre-Emerick Aubameyang is 3/1 to score first.
Wembley has been a problem for Tottenham in Europe.
Their only victory on their adopted turf came against CSKA Moscow, who did not win a game.
But if Spurs thought last year's group was difficult, the latest draw has been even tougher on them.
Real Madrid and Borussia Dortmund as the first and second seeds is about as challenging as it gets and Spurs have little room for error: they start against Dortmund, who they will likely compete with for second place behind Madrid, at home.
Anything but a win immediately gives the German side the edge and will leave Tottenham almost certainly needing to either get a result against Madrid or at Signal Iduna Park in the return clash.
There is more European experience in Spurs' ranks this year. Serge Aurier could debut, while Davinson Sanchez is in contention to face his old coach and Fernando Llorente is no newcomer to this competition.