While Hoffenheim have lost three of their last five, Stuttgart are on a five-game losing streak since the turn of the year, and have been beaten eight times in their last 10 outings.
As a result, both are in acute relegation danger ahead of their match at the Rhein-Neckar Arena.
"Everybody must understand how much is at stake," said Stuttgart coach Thomas Schneider.
"We need a team to turn the corner; a team which puts their individual egos to one side."
If Stuttgart remain in a rut, Schneider's future could be called into question, even if there have yet to be any major calls for him to be dismissed.
Schneider has not heard any, although he admits he has not spent much time in public recently.
"I've turned to home delivery," he said, keeping a sense of humour in spite of his side's predicament.
A further problem for Stuttgart sees them deprived also of top scorer Vedad Ibisevic for the next five games due to suspension.
Ibisevic's Bosnian compatriot Sejad Salihovic will be in action for Hoffenheim.
The Hoffenheim vice-captain is preparing for a battle which he hopes to win.
"We know how important this game is for us," Salihovic said on his club's website. "We've got good lads who are really going to get stuck in. I'm not concerned. We'll be fully fit and ready."
Hoffenheim were knocked out of the DFB-Pokal by Wolfsburg in midweek, meaning all of their efforts will be focused on rising away from the danger zone and avoiding a repeat of last season's dramatic survival battle.
"This game is more important than Wednesday's," said Salihovic. "A win would give us a bit of breathing room. It's a derby and will be intense."