The network said the adventure film, to be directed by Jonathan Frakes, is set to air this winter.
Bruce Davison and Stana Katic will co-star in the made-for-TV movie.
Wyle, Newhart and Curtin previously starred in the wildly popular "The Librarian: Return to King Solomon's Mines" and "The Librarian: Quest for the Spear."
The new installment finds hero/librarian Flynn (Wyle) led by strange dreams to New Orleans where he finds himself uncovering a conspiracy involving the notorious vampire, Prince Vlad Dracul, TNT said.
Once again, Flynn must overcome his fears and protect one of the world's most sacred artifacts -- this time the Judas Chalice -- or face the consequences of allowing it to fall into the wrong hands, the network said.