This quarter-final tie will be a repeat of the 2006-07 final, which Nuremberg triumphed 3-2 after extra-time to deny their opponents a domestic double.
Match preview
Nuremberg have fallen significantly in the ensuing 16 years since their last major cup triumph, of course, having only competed in the Bundesliga for one season since their relegation at the end of the 2013-14 campaign.
That most recent top-flight appearance came in the 2018-19 season, when they were instantly relegated back to Germany's second tier alongside their forthcoming opponents.
Currently sitting in 13th place in the second tier - and only three points clear of the relegation zone - Der Club do not appear likely to return to the Bundesliga any time soon under Dieter Hecking's tutelage.
However, making it through to the last four of Germany's main domestic cup for the first time since their famous success in 2007 would clearly represent a major achievement for a side competing outside of the elite division, and they will feel confident of history repeating itself at Max-Morlock-Stadion on Wednesday.
Indeed, Stuttgart are desperately fighting to avoid potentially joining Nuremberg in the second tier next season, with their 3-0 defeat to Union Berlin at the weekend leaving them bottom of the table.
Bruno Labbadia has failed to make the desired impact both he and the club's hierarchy would have hoped for when appointing him as manager in December, with the 57-year-old collecting only six points from his 11 league games in charge so far.
Moreover, Hoffenheim's victory against Werder Bremen on Sunday means that Stuttgart are now five points adrift of safety, although Labbadia's former club Hertha Berlin are only two points ahead of them in the relegation play-off spot.
Stuttgart's players may be relishing the prospect of playing in a different competition in midweek, then, as they look to go one better than their predecessors at the club, who have lost out in the DFB-Pokal final on two occasions since last winning the competition in 1997.
Nuremberg DFB-Pokal form:
W
W
W
Nuremberg form (all competitions):
L
W
L
W
D
L
Stuttgart DFB-Pokal form:
W
W
W
Stuttgart form (all competitions):
W
L
L
D
L
L
Team News
Nuremberg will remain without Lukas Schleimer and Erik Wekesser due to long-term knee injuries, while Christian Mathenia is unlikely to recover from a shoulder issue in time to feature.
After blanking in a 1-0 defeat to Darmstadt in their most recent league match, Hecking may be tempted to hand Danny Blum and Erik Shuranov a chance in attack, while Florian Flick could come into the hosts' engine room in midfield.
Stuttgart, meanwhile, appear likely to travel without key players Borna Sosa and Silas after the duo both missed their side's trip to Berlin at the weekend due to muscle injuries.
However, Serhou Guirassy made his comeback from the bench during the 3-0 defeat, with the forward likely to start on Wednesday. That is unlikely to be Labbadia's only change given how poor his side's performance and result was.
Nuremberg possible starting lineup:
Vindahl-Jensen; Gyamerah, Hubner, Schindler, Brown; Duman, Flick, Geis, Tempelmann, Shuranov; Blum
Stuttgart possible starting lineup:
Muller; Stenzel, Mavropanos, Zagadou, Ito; Haraguchi, Endo, Karazor; Dias, Guirassy, Fuhrich
We say: Nuremberg 2-1 Stuttgart
Stuttgart appear to be ripe for the picking at the hands of an upset to Nuremberg, who will feel the weight of history on their side after the events of the 2006-07 final.
Neither team's league campaigns have gone as they would have hoped for, but with Max-Morlock-Stadion set to welcome far more fans within its 50,000-capacity than usual, the hosts could defy their standing in Germany's footballing pyramid to make the last four.