The tie is finely poised after a 1-1 draw was played out in the first leg in the Netherlands three weeks ago, with Luuk de Jong's second-half penalty cancelling out an early opener from ex-PSV man Donyell Malen.
Match preview
Five days after sharing the spoils with PSV, Dortmund were beaten 3-2 at home to Hoffenheim in the Bundesliga, but they have since bounced back with consecutive wins away from home against Union Berlin and Werder Bremen.
After securing a routine 2-0 success in Berlin, BVB battled to a 2-1 victory with 10 men against Bremen last weekend courtesy of first-half goals from Malen and Jadon Sancho - the latter netting his first goal since re-joining the club on loan from Manchester United.
The dismissal of Marcel Sabitzer on the stroke of half time allowed Bremen back into the game, with Justin Njinmah reducing the deficit 20 minutes from time, but Dortmund held on to claim all three points and remain fourth in the Bundesliga table, just one point above fifth-placed RB Leipzig with nine games remaining.
Edin Terzic's side now turn their attention to their sixth Champions League knockout campaign in eight seasons, but only once in the last six years have they advanced to the quarter-finals. However, BVB have progressed from their last five knockout ties in the competition when they have avoided defeat in an away first leg.
The German outfit head into Wednesday's second leg following an indifferent run of form on home soil, having come out on top in only four of their last nine matches at Westfalenstadion in all competitions, but they are unbeaten in their last eight Champions League home games, which bodes well ahead of the visit of PSV.
Since drawing the first leg with Dortmund, PSV have accumulated seven points from three Eredivisie fixtures, following up a thumping 7-1 win at PEC Zwolle and 2-2 home draw with Feyenoord with a slender 1-0 victory away against Go Ahead Eagles last weekend.
Sergino Dest scored the only goal of the closely-fought contest in the 10th minute - PSV's 80th top-flight strike in their 25th game of the campaign - to help the Red and Whites preserve their impressive unbeaten league run and maintain their 10-point lead at the summit over second-placed Feyenoord.
PSV's heavy 4-0 loss at Arsenal in the Champions League group stage is one of only two defeats suffered by Peter Bosz's side in 39 matches across all tournaments so far this season, but their resolve is set to be put to the test by Dortmund on Wednesday.
Indeed, PSV travel to Westfalenstadion having failed to win any of their previous 16 visits to Germany in all competitions, losing on 13 occasions; they have lost five of their last six such matches in the Champions League, while their last-ever triumph in Germany was against Eintracht Braunschweig back in December 1977.
PSV did, however, play out a 1-1 draw in their only previous visit to Dortmund back in October 2002, and considering they have won their last three domestic away games by an aggregate score of 13-2, there is reason for Bosz and co to be optimistic of securing their place in the Champions League quarter-finals for the first time since 2006-07.
Borussia Dortmund Champions League form:
D
W
W
W
D
D
Borussia Dortmund form (all competitions):
W
D
D
L
W
W
PSV Eindhoven Champions League form:
D
D
W
W
D
D
PSV Eindhoven form (all competitions):
W
W
D
W
D
W
Team News
Borussia Dortmund's only two injury concerns are with attackers Sebastien Haller and Samuel Bamba, who remain sidelined with respective ankle and muscle problems.
Felix Nmecha recovered from a hip injury to make a substitute appearance last time out and the midfielder will be pushing to start on Wednesday ahead of either Sabitzer or Emre Can.
Mats Hummels could replace Niklas Sule and partner Nico Schlotterbeck in central defence, while Karim Adeyemi and Marco Reus are set to battle with Sancho and Julian Brandt for starts in the final third along with Malen, whose first-leg goal made him the first Dutch player to score against a Dutch team in the knockout stages of the Champions League.
As for PSV, Noa Lang is ruled out for an extended period with a hamstring injury, while Joey Veerman and Ismael Saibari, who were both absent from last weekend's win at Go Ahead Eagles, are both doubtful with muscle injuries and will be assessed ahead of kickoff.
Guus Til, Mauro Junior and Malik Tillman are all options to start in centre-midfield alongside Jerdy Schouten if Veerman and Saibari are not deemed fit to feature.
Tillman, however, could be replaced by star winger Johan Bakayoko, who was rested at the weekend, with the Belgian set to join Hirving Lozano and top scorer De Jong - who has contributed with seven goals and four assists in his last eight appearances - in a three-man attack.
Borussia Dortmund possible starting lineup:
Kobel; Ryerson, Hummels, Schlotterbeck, Maatsen; Sabitzer, Can; Malen, Brandt, Adeyemi; Fullkrug
PSV Eindhoven possible starting lineup:
Benitez; Teze, Obispo, Boscagli, Dest; Schouten, Til, Junior; Bakayoko, De Jong, Lozano
We say: Borussia Dortmund 2-2 PSV Eindhoven (a.e.t, Borussia Dortmund to win on penalties)
There was little to separate Dortmund and PSV three weeks ago, and another closely-contested encounter could be on the cards on Wednesday between two teams who will be confident in their own abilities to advance to the last eight.