Former top models Derek and Hansel, both living in seclusion after a tragic accident at the "Derek Zoolander Center For Kids Who Can't Read Good" claimed the life of Matilda, are lured back into the high-fashion world by Billy Zane. Now, an Interpol agent named Valentina Valencia seeks their help to investigate the mysterious assassinations of several pop stars. These pop stars have died with Derek's iconic "Blue Steel" look on their faces, sparking speculation that they hold the key to unraveling a deeper conspiracy centered on a secretive fashion cabal.

As Derek and Hansel navigate their return to modeling and reluctantly embrace their roles as amateur sleuths, they encounter various outlandish characters, including familiar faces from their past. Their quest to uncover the truth leads them through a maze of betrayals, revelations, and absurd scenarios. The duo also seeks redemption for their personal failures along the way, all while contending with their own insecurities and the outlandish demands of the fashion world's elite. The story continues to unfold with twists and comedic segments, building up to a climax where the true nature of the conspiracy is uncovered.