Not only do Hoffenheim need to beat the outgoing Bundesliga champions on their own soil - a week before they face Bayern Munich in the Champions League final - but they also must hope that one of either Augsburg or Fortuna Dusseldorf lose their matches against Greuther Furth and Hannover respectively.
The most unlikely part of the escape equation is Hoffenheim overcoming Jurgen Klopp's men and Gisdol is calling on his players to keep their nerve.
"The only way you can survive in Dortmund is if everything comes together," he said.
"We're not going to get many chances, but we've got to keep our composure with the ones we do get."
It could be Hoffenheim's last trip to the imposing Westfalenstadion for a while, but defender Jannik Vestergaard insists his side will not be intimidated.
"It's every young footballer's dream to measure yourself with the best, and to do that in front of 80,000 fans - the joy of being involved in this game far outweighs everything else," he said on his club's website.
The stakes may not be so high for Dortmund, who have already secured second spot in the Bundesliga.
Their priority is to come through this final league game of the season unscathed before turning their attention to next weekend's showcase at Wembley.
"I hope everybody sticks to the rules," Klopp said at a press conference.
"Hard but fair, and then let's play some good football."
Klopp may rotate his side in view of next Saturday, but has made it clear that they want to win the game.
"There's no doubt about it," he said. "We need to pick up our rhythm again."