Dortmund's weekend win lifted them to second in the table, their highest position of the season so far, and nine points adrift of Bayern Munich at the summit.
Victory at the Westfalenstadion on Tuesday would reduce that deficit to six points, at least for 24 hours. And, with the two clubs then due to meet at the Allianz Arena on Saturday, the Westphalians have the chance to throw the title race wide open in an important week.
Dusseldorf, on the other hand, will not be intimidated having won for the first time at their Dusseldorf Arena on Friday night.
"We have got nothing to lose there and we can play without any pressure," striker Stefan Reisinger said.
It was a similar scenario a year ago when the two sides last met, in the last 16 of the DFB-Pokal in the North-Rhine Westphalian capital.
Dusseldorf pushed the eventual cup winners all the way, eventually capitulating in a penalty shoot-out, while their head-to-head record also gives them no reason to feel inferior.
Both sides have won 18 times with eight draws, setting the scene for a very balanced encounter in Dortmund, only the hosts could be without a key player in Ilkay Gundogan.
"I hope it's not so bad," Dortmund coach Jurgen Klopp said after the Germany international picked up an ankle injury at the weekend.
"His ankle has not swollen too much, but it's going to be touch and go for the Fortuna game."