The Ligue 1 leaders have excellent history in the competition, which they last won in 2008 with a 2-1 victory over Lens.
That triumph secured a third Coupe de la Ligue title for PSG and Laurent Blanc's men will be heavy favourites to secure another final appearance, against Lyon or Troyes.
The defending French champions have already beaten Nantes twice this season, the latest win a 5-0 drubbing at the Parc des Princes on January 19.
However, PSG will likely have to cope on this occasion without striker Edinson Cavani, who looks set for a spell on the sidelines after sustaining a thigh injury in Friday's 2-0 home win over Bordeaux.
Midfielder Marco Verratti should return after missing the Bordeaux game through suspension, but Adrien Rabiot (knee) and Christophe Jallet (back) are unlikely to figure.
Striker Fernando Aristeguieta, midfielder Johan Audel and winger Fabrice Pancrate (all thigh) are expected to miss out for Nantes, along with attacking midfielder Banel Nicolita (groin).
Nantes, Coupe de la Ligue winners in 1965, last reached the final in 2004 only to be beaten on penalties by Sochaux.
Michel Der Zakarian's men won a thriller to qualify for the last four this season, Serge Gakpe's 87th-minute goal securing a 4-3 win over Nice.
PSG's trip to the Stade de la Beaujoire comes during a crucial week for Blanc's side, who visit Ligue 1 title rivals Monaco next Sunday.
And winger Lucas Moura has been quick to stress the importance of the upcoming fixtures.
"There are very important matches to come starting with Tuesday," Lucas told PSG's official website.
"(It is) a meeting that can allow us to play in a final. Let's work and prepare (for) this match."
The second semi-final between Lyon and Troyes takes place 24 hours after Nantes' meeting with PSG.
