The two teams are in Group H, which has been labelled this season's 'Group of Death' as it also contains current champions Real Madrid, who face APOEL in the Spanish capital.
It is therefore of prime importance for both Mauricio Pochettino's men and Peter Bosz's side to not take the occasion lightly as it could ultimately decide who progresses to the knockout stages.
Spurs will be without star midfielder Dele Alli as he serves a three-match ban for his terrible challenge on Gent's Brecht Dejagere in the Europa League last term.
The hosts may look to attack down the left flank as Dortmund are without Schmelzer, Bartra, Durm and Guerreiro, who are all sidelined with injuries.
To add to the German side's worries, Julian Weigl (ankle), Andre Schurrle (thigh), Sebastian Rode (knock), Marco Reus (knee), Erik Durm (hip) and Raphael Guerreiro (foot) also miss out, putting the club in an early injury crisis.
They do, however, possess a frightening attack. Mario Gotze, Christian Pulisic and Pierre-Emerick Aubameyang will likely be the men tasked with breaking down a solid Spurs back line.
Possible lineups:
Tottenham: Lloris; Alderweireld, Sanchez, Vertonghen; Aurier, Dier, Dembele, Davies; Son, Eriksen; Kane.
Borussia Dortmund: Burki; Piszczek, Papastathopoulos, Toprak, Zagadou; Sahin, Castro, Gotze; Philipp, Pulisic; Aubameyang.