<p>Neutrophils are the most abundant type of white blood cells in the immune system and play a complex and intricate regulatory role in disease progression. Their critical contribution to maintaining homeostasis through migration, activation, and programmed cell death is indispensable. In contrast to traditional nanocarrier-based drugs, smart nanomaterials capable of precisely targeting distinct stages of neutrophil development can dynamically regulate drug distribution in both time and space while controlling the fate of neutrophils during migration, activation, and apoptosis. This enables the realization of precise and personalized disease diagnosis and treatment. Therefore, this review introduces a state-of-the-art framework for intelligent nano-immune engineering, wherein artificial intelligence-driven nano-design, dynamic response systems, and biomimetic materials science are integrated into the spatiotemporal reprogramming of neutrophil fate. We analyze stage-specific targeting strategies that are computationally learned, biologically validated, and synthetically optimized, while highlighting their emerging applications in precision therapy. By synergistically merging materials science, immunology, and intelligent technologies, we aim to offer novel perspectives on the advancement of the burgeoning field of “intelligent nano-immune engineering” and lay a solid foundation for the development of next-generation intelligent therapeutics.</p> Graphic abstract <p></p>