bundesliga.com previews the action at the Stadio San Paolo, where the Wolves will take to the field trailing 4-1 from the first leg...
The victors in this tie will have knocked out a potential competition winner, but a place in the last four is not the only incentive driving these sides on. The final in Warsaw on 27 May will just be two games away, with a place in next season's UEFA Champions League on offer for the eventual tournament winners.
Napoli coach Rafael Benitez, a winner of this competition with Valencia CF in 2004 and Chelsea FC in 2013, will be without Camilo Zuniga and Michu (l.), both out with knee complaints, while Christian Maggio is a doubt with flu. Otherwise, the Spaniard's squad has a clean bill of health.
Dieter Hecking, meanwhile, will be missing arguably his best player in Kevin De Bruyne (foot), while Andre Schürrle (shoulder), Aaron Hunt (knee) and Vieirinha (flu) are also unavailable. Ivan Perisic will start, while Hecking must decide between Bas Dost and Nicklas Bendtner as his lone striker.
On the evidence of his performance in the first leg, the Wolves will do well to shackle striker Gonzalo Higuain if they are to have any chance of upsetting the odds. The Argentine international scored the first and assisted the second in last week's first leg, with the Wolves unable to deal with his pace and movement.
In the absence of De Bruyne, the creative burden will be on Perisic to turn things around for Wolfsburg. The Croatian has only just returned from injury, but is a dangerous player on either wing and is always prepared to take risks, as he showed in assisting Bendtner's consolation effort last week.
Benitez: "We know that Wolfsburg have a strong team - they scored four against FC Bayern not so long ago. They are dangerous in attack and that's where we need to be careful. We have to play just as well as we did in Germany."
Hecking: "We're not overly optimistic after the first leg and we have some players missing, but we also have a great squad. We know we can beat anyone on our day, but we also have to remember that it'll be extremely difficult. We'll give it our best, though."
Hecking's charges endured a frustrating return to action after the first leg, dominating against FC Schalke 04 at the weekend but only managing a 1-1 draw. Napoli, fourth in the Serie A table, enjoyed a comfortable 3-0 win at Cagliari Calcio at the weekend.
Last week's first leg was the first time these clubs had met in a competitive game. Wolfsburg's defeat of FC Internazionale Milano in the last round was their second meeting against Italian opponents, the previous coming against AC Milan in 2008/09. Before last week, Napoli had lost their last four matches on German soil.
Napoli: Andujar - Maggio, Albiol, Britos, Ghoulam - López, Inler - Gabbiadini, De Guzman, Mertens - Zapata
Wolfsburg: Benaglio - Träsch, Knoche, Naldo, Rodriguez - Guilavogui, Luiz Gustavo - Caligiuri, Arnold, Perisic - Dost