The two clubs, who will be playing out a repeat of the 1997 UEFA Cup final which the Germans won 1-0, are both mired in domestic woes that have overshadowed the build-up to a tie defending champions Inter are favourites to win.
Inter, treble winners last season under Jose Mourinho, are still brooding following Saturday's 3-0 loss to rivals AC Milan which all but ended their hopes of a sixth successive scudetto and exposed coach Leonardo's technical failings.
Schalke, a modest 11th in the Bundesliga, have progressed to the last eight for only the second time, yet this was almost lost in the confusion surrounding the sacking of coach Felix Magath only a week after they beat Valencia in the last 16.
Magath was fired in mid-March with club chairman Clemens Toennies saying there were "very good reasons" but refusing to elaborate.
However, the famously die-hard supporters had become increasingly critical of Magath's far-reaching powers and controversial transfers while the team's shaky domestic form did not help either.
Schalke striker Raul, who is hoping to add a fourth Champions League medal to the three he won at Real Madrid, has promised he will see out his contract, which runs until 2012, despite the exit of the man who lured him to Gelsenkirchen.
Ralf Rangnick has returned for a second stint at the club and made his debut on Friday in the uncompleted Bundesliga match at St Pauli which was halted by crowd violence with Schalke leading 2-0.
Inter's Argentine midfielder Javier Zanetti, the only survivor of the 1997 meeting on either side, called on his team mates to put Saturday's disappointment behind them.
"It's not nice to lose that type of game, it' a disappointment to everyone but we have to look forward," he told Inter's website ahead of the first leg.
Inter's Brazilian central defender Lucio is suspended with Colombian Ivan Cordoba expected to take his place alongside Andrea Ranocchia in the centre of the defence.
Schalke 04's defender Christoph Metzelder suffered a broken nose against St Pauli but may play with a protective face mask.
However, the Germans will be without striker Mario Gavranovic, with torn ankle ligaments, and midfielder Peer Kluge, with a stomach injury.
Kluge's injury is an added worry for Rangnick as Ghana midfielder Anthony Annan, his natural replacement, is not eligible for the Champions League.
Inter Milan: 1-Julio Cesar; 13-Maicon, 2-Ivan Cordoba, 15-Andrea Ranocchia, 26-Cristian Chivu; 4-Javier Zanetti, 17-Esteban Cambiasso, 8-Thiago Motta; 10-Wesley Sneijder; 9-Samuel Eto'o, 27-Goran Pandev
Schalke 04: 1-Manuel Neuer; 22-Atutso Uchida, 4-Benedikt Hoewedes, 21-Christoph Mezelder, 3-Sergio Escudero; 13-Lukas Schmitz, 32-Joel Matip, 8-Carlos Jurado, 25-Klaas-Jan Huntelaar; 17-Jefferson Farfan, 7-Raul
Referee: Martin Atkinson (England)
