The Lilywhites will be hoping to avoid the nightmare start that they endured 12 months ago, when the concession of two goals in the last five minutes gifted Inter Milan a 2-1 victory at the San Siro.
This was the beginning of a run that saw Spurs struggling with just one point from their opening three matches in Group B last season. The side from N17 then turned it around in dramatic fashion as they carved together a miracle run to the final before being beaten by Liverpool in Madrid.
Last year's finalists have been blighted by injuries in the opening weeks of the campaign, with Pochettino having had to be creative with his use of different formations and personnel.
Here, Sports Mole looks at how Tottenham could line up for Wednesday's match.
Despite still having a number of players sidelined, Mauricio Pochettino does have different options on how he could approach this match.
Saturday's win over Palace saw the overdue return of Serge Aurier to the starting XI, and the Ivorian is likely to retain his place at right-back.
On the opposite flank, Ben Davies could be handed his first start of the season. Pochettino often likes to rotate his full-backs for midweek fixtures, and the Welshman has been restricted to just two brief cameos from the bench this season.
With Sanchez and Foyth both injured, Alderweireld and Vertonghen will retain their places at centre-back. Ahead of them, Harry Winks could drop out to allow record signing Tanguy Ndombele back into the team.