Ange Postecoglou has secured a return to continental football for the Premier League giants through their fifth-placed finish in 2023-24.
Although there was disappointment in missing out on the Champions League, the North Londoners begin the second-tier competition as one of the favourites to lift the trophy.
The newly-formed league phase of this tournament commences on Wednesday night, with the games split over that evening and Thursday.
Spurs have been presented with some eye-catching fixtures, a home encounter against Roma and a trip to Rangers on the agenda before the end of January.
However, Postecoglou and his side will first take on Azerbaijani opposition in the form of Qarabag, who find themselves in this competition having lost out in Champions League qualifying.
Why is Romero missing for Spurs?
While Postecoglou will naturally rotate his squad for the contest at the Tottenham Hotspur Stadium, Cristian Romero may have been in contention to start had he been available.
With Spurs having not participated in Europe during the last campaign, it has largely been forgotten that the Argentina international is unable to take to the pitch versus Qarabag.
That is a result of Romero having been sent off in Spurs' last European fixture, a Champions League last-16 encounter at home to AC Milan.
Romero received two yellow cards on that occasion, the dismissal and subsequent one-match ban remaining on his record for last season and the ongoing one.
As a result, the 26-year-old will not be able to feature in a European fixture this term until the trip to Ferencvaros next week.
Who will line up in defence?
Postecoglou must now decide whether to risk Micky van de Ven in a contest that where he would usually rest the Dutchman, particularly with Manchester United to come at the weekend.
The likelihood is that Radu Dragusin and Ben Davies will be used in the middle of the backline, providing that Destiny Udogie is used at left-back instead of the latter.