Jurgen Klopp's side will be hoping to bounce back from their defeat to Real Madrid in midweek and avenge their loss at the Volkswagen Arena earlier this season
Following a run of four games without defeat, Wolfsburg sit just outside the Champions League places - a point behind fourth-placed Bayer Leverkusen.
Anything other than a Leverkusen victory at Hamburg on Friday would allow Wolfsburg to move into the top four and improve their chances of reaching Europe's premier club competition for only the second time in their history.
While they face a Dortmund side second in the table, eager to finish above rivals Schalke, Jurgen Klopp's men could still be reeling from Wednesday's 3-0 Champions League loss at the Bernabeu.
Not only did the defeat highlight how much injuries have hampered Dortmund this term compared to last season when they beat Madrid over two legs, it also saw goalkeeper Roman Weidenfeller and attacker Marco Reus pick up further knocks.
They are doubts for Klopp as he looks to help secure Dortmund's place in next season's Champions League against a Wolfsburg team who won the reverse fixture 2-1 at the Volkswagen Arena.
That loss was the second of three in a row during November for Dortmund, whose form has been generally impressive since the turn of the year.
And Klopp is determined to ensure that his side finish runners-up behind Bayern Munich.
"We want to finish second, I've said [before]. I couldn't care less who finishes third," he said.
"Wolfsburg have some tough games coming up, not just against us. There is pressure on every game right now."
Having recovered from a blip at the start of March, which saw them ship 12 goals in two games against Hoffenheim and Bayern Munich, Wolfsburg have steadied the ship somewhat.
Dieter Hecking's charges have not tasted defeat against Dortmund in their last three meetings and the coach is eager to secure Champions League qualification.
"We want to be fourth. We want to seize the opportunity," he said this week.
Experienced striker Ivica Olic, who scored the winner when the sides last met, echoed the thoughts of his coach, saying: "Of course, it would be a great dream if we can achieve that at the end of the season.
"If we carry on like this, anything is possible."