Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with limited treatment options. The development of tagraxofusp, a CD123-directed recombinant fusion protein, has revolutionized the management of BPDCN. This manuscript reviews the current understanding of BPDCN pathophysiology, clinical presentation, and diagnostic challenges. We delve into the mechanisms of action of tagraxofusp, explore its clinical efficacy and safety profile, and discuss its role as a potential frontline and salvage therapy. Additionally, we highlight ongoing research and future directions to optimize the use of tagraxofusp in BPDCN treatment.