However, the Gunners have been in very poor form of late, with no wins in their last six games across all competitions, and pressure is beginning to pile on manager Unai Emery.
Arsenal did run out comfortable winners the last time these two met, though, claiming a 3-0 victory over their German opponents following a late red card for Frankfurt.
Here, Sports Mole looks at how the Gunners could line up for Thursday's showdown.
Emery is expected to make sweeping changes to the side that drew 2-2 at home against Southampton, as he has regularly done for cup games.
Emiliano Martinez will expect to take Bernd Leno's place between the sticks, but if Kolasinac's injury keeps him out then left-back Kieran Tierney could be among the few to retain his spot from the last match.
Shkodran Mustafi could come in at centre-back, while Holding's potential injury could open the door for Konstantinos Mavropanos to make a rare start alongside the German. Calum Chambers could be another to keep his place in the side, being shuffled out to right-back if Emery chooses to return to a back four.
In the centre of the park, Joe Willock will expect to be given an opportunity, with Ceballos out and Matteo Guendouzi likely to be rested. Combative midfielder Lucas Torreira could start alongside the youngster to provide balance to the midfield.
Ahead of them, Reiss Nelson, Emile Smith Rowe and Ainsley Maitland-Niles are likely to play as the attacking trio behind impressive new signing Gabriel Martinelli, with Saka not likely to be risked and allowing Mesut Ozil, Pierre-Emerick Aubameyang and Alexandre Lacazette an opportunity to be rested.