Basel stormed to a 3-0 victory in the first leg and - barring any disasters - can look forward to reaching the last eight of the competition for the first time since the 2013-14 campaign.
Basel managed to string together a six-game unbeaten run during the final stretch of the Swiss Super League campaign, but the 20-time national champions were forced to settle for third as Young Boys retained their title with relative ease in the 2019-20 season.
Basel's campaign drew to a close with three successive draws, as an eight-goal thriller with Lugano was followed up with goalless stalemates against Thun and Luzern in their final trio of matches.
However, Marcel Koller's side must now put their domestic disappointment behind them as they look to win their fifth Europa League game in succession and advance to the quarter finals.
Bebbi ought to feel confident of reaching the last eight having enjoyed a comfortable 3-0 victory over Frankfurt in the first leg, with goals from Samuele Campo, Kevin Bua and Fabian Frei giving Basel the upper hand in the tie back in March.
Furthermore, Koller's men are yet to concede a goal in the Europa League since the turn of the year, and Basel are aiming to set up a quarter-final tie with one of either Wolfsburg or Shakhtar Donetsk.
Likewise, Frankfurt's Bundesliga campaign ultimately ended in disappointment as they finished ninth despite their strong end to the season.
Adi Hutter witnessed his side pick up three wins from their last four domestic outings, but the damage was done earlier in the campaign and Frankfurt will go without European football next season unless they can go all the way in the 2019-20 Europa League.
Overturning a 3-0 deficit in Basel's own backyard is certainly difficult, but not impossible, and Hutter will hope to see his side carry over the momentum from their strong end to the Bundesliga season when they make the relatively short journey to Switzerland on Thursday.
Frankfurt have taken to the pitch just once since the Bundesliga season drew to a close, with Die Adler playing out a 1-1 draw with Monaco in a friendly on the first day of August.
Basel Europa League form: WLWWWW
Basel form (all competitions): WDWDDD
Frankfurt Europa League form: LWLWDL
Frankfurt form (all competitions): LLWWDW
Basel goalkeeper Jonas Omlin - who has kept 16 clean sheets for the Swiss outfit across all competitions this season - has struggled with a hamstring issue recently and may not feature here.
With regards to Frankfurt, Hutter will be hopeful of having Makoto Hasebe back in time for the second leg, with the defender recently undergoing knee surgery in his native Japan.
However, Djibril Sow is suspended for the Bundesliga outfit after picking up his third yellow card of the Europa League campaign in the first-leg defeat.
Stefan Ilsanker could therefore come in to partner Sebastian Rode in midfield, and Hutter could revert back to his tried-and-tested three-man defence after lining up with a four-at-the-back system in the first leg.
Basel possible starting lineup:
Nikolic; Widmer, Comert, Alderete, Riveros; Xhaka, Frei; Stocker, Campo, Petretta; Cabral
Frankfurt possible starting lineup:
Trapp; Abraham, Hasebe, Hinteregger; Costa, Rode, Ilsanker, Kostic; Kamada; Silva, Dost
We say: Basel 1-1 Frankfurt
Frankfurt were simply outclassed in the first leg and must now navigate the difficult task of putting four past a Basel side that have kept clean sheets in their last four Europa League outings. We are expecting a more closely-fought game in the second leg, but Basel should do enough to book their spot in the quarter finals.