Ange Postecoglou will know this competition is boom or bust for Spurs, and likely his job, as they look to not only navigate past the German outfit but lift the trophy in May.
Spurs have produced some of their better performances in the Europa League this season but will know the same can be said for Frankfurt, who sit third in the Bundesliga.
It is the biggest game of the season so far for Spurs, with next week’s second leg likely topping it, and anything less than a win will pile even more pressure on Postecoglou.
Tottenham's injury woes of the last few months are almost behind them, but they will still be without Dejan Kulusevski, Kevin Danso and Radu Dragusin for Thursday's first leg. It remains to be seen if Kulusevski and Danso will be fit for next week's second leg, but Dragusin is out for the rest of the season.
Spurs will be able to call upon Rodrigo Bentancur, who has served a one-game Europa League ban, while Micky van den Ven and Destiny Udogie are expected to start after being rested at the weekend. Ange Postecoglou has a few decisions to make in attack, namely who starts on the right wing between Brennan Johnson and Wilson Odobert
Frankfurt will have second-choice goalkeeper Kaua Santos in goal as Kevin Trapp has failed to recover from injury. Elye Wahi is also sideline, but Igor Matanovic is back in contention after two months out.
Striker Hugo Ekitike is the big danger for the Bundesliga side, after Omar Marmoush left for Manchester City in January, and he will be supported by Mario Gotze, who is now 32 years old but still a potent threat from midfield.
Tottenham prepared for this game with a lacklustre 3-1 win over Southampton, which saw them not needing to exert much energy - or attempt to do so. It remains to be seen if they can glean any momentum from the result, but the come fit and firing for the visit of Frankfurt.
Frankfurt's form has certainly taken a knock since Marmoush's exit, they have won just five of 13 games since his move was confirmed, but their Europa League form continues to impress. This will be a tight tie over two legs, with Spurs to edge the first in front of their own fans.