Neutrophils, the most abundant white blood cells in the circulation, play a dual role in cancer development and progression. They can either act as anti-tumor (N1) or pro-tumor (N2) cells, depending on their phenotype and function. N1 neutrophils exhibit anti-tumor properties, such as tumor cell-killing and immunostimulatory activities, while N2 neutrophils promote tumor growth, metastasis, and immunosuppression. Recent advancements in single-cell sequencing have enhanced our understanding of the phenotypic heterogeneity and functional plasticity of neutrophils in cancer. Engineering neutrophils for drug delivery and targeting the tumor microenvironment (TME) represents a promising approach in cancer therapy. Neutrophils and their derivatives, such as membranes and extracellular vesicles (EVs), have been used to enhance the delivery of drugs, nanomaterials, and therapeutic molecules to tumors. These engineered neutrophils and EVs offer improved stability, inflammation responsiveness, and tissue penetration, leading to enhanced therapeutic efficacy. The anti-tumor potential of neutrophils is attributed to their secretion of cytotoxic substances, activation of anti-tumor immune responses, and antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can suppress metastasis, kill cancer cells, and inhibit tumor growth through various mechanisms, including the production of reactive oxygen species (ROS) and nitric oxide (NO). They also stimulate T cell responses and enhance anti-tumor immunity. In contrast, N2 neutrophils promote tumor progression by enhancing tumor cell proliferation, angiogenesis, and metastasis. They secrete pro-metastatic proteins, induce epithelial-to-mesenchymal transition (EMT), and inhibit immune surveillance. Neutrophils also contribute to therapy resistance by recruiting regulatory immune cells and promoting immunosuppression. Neutrophil-based drug delivery systems, such as living cell drug delivery systems, coated nanoparticles (NPs), and EVs, have shown significant potential in cancer therapy. These systems can enhance the delivery of drugs to tumors, improve therapeutic efficacy, and reduce systemic toxicity. For example, neutrophils loaded with photodynamic therapy (PDT) or photothermal therapy (PTT) agents have been shown to effectively target and treat tumors. Additionally, combining neutrophil-based delivery systems with other therapeutic modalities, such as chemotherapy and radiotherapy, has demonstrated enhanced anti-tumor effects. Overall, the engineering and targeting of neutrophils for cancer therapy offer a promising avenue for improving treatment outcomes and reducing side effects.Neutrophils, the most abundant white blood cells in the circulation, play a dual role in cancer development and progression. They can either act as anti-tumor (N1) or pro-tumor (N2) cells, depending on their phenotype and function. N1 neutrophils exhibit anti-tumor properties, such as tumor cell-killing and immunostimulatory activities, while N2 neutrophils promote tumor growth, metastasis, and immunosuppression. Recent advancements in single-cell sequencing have enhanced our understanding of the phenotypic heterogeneity and functional plasticity of neutrophils in cancer. Engineering neutrophils for drug delivery and targeting the tumor microenvironment (TME) represents a promising approach in cancer therapy. Neutrophils and their derivatives, such as membranes and extracellular vesicles (EVs), have been used to enhance the delivery of drugs, nanomaterials, and therapeutic molecules to tumors. These engineered neutrophils and EVs offer improved stability, inflammation responsiveness, and tissue penetration, leading to enhanced therapeutic efficacy. The anti-tumor potential of neutrophils is attributed to their secretion of cytotoxic substances, activation of anti-tumor immune responses, and antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can suppress metastasis, kill cancer cells, and inhibit tumor growth through various mechanisms, including the production of reactive oxygen species (ROS) and nitric oxide (NO). They also stimulate T cell responses and enhance anti-tumor immunity. In contrast, N2 neutrophils promote tumor progression by enhancing tumor cell proliferation, angiogenesis, and metastasis. They secrete pro-metastatic proteins, induce epithelial-to-mesenchymal transition (EMT), and inhibit immune surveillance. Neutrophils also contribute to therapy resistance by recruiting regulatory immune cells and promoting immunosuppression. Neutrophil-based drug delivery systems, such as living cell drug delivery systems, coated nanoparticles (NPs), and EVs, have shown significant potential in cancer therapy. These systems can enhance the delivery of drugs to tumors, improve therapeutic efficacy, and reduce systemic toxicity. For example, neutrophils loaded with photodynamic therapy (PDT) or photothermal therapy (PTT) agents have been shown to effectively target and treat tumors. Additionally, combining neutrophil-based delivery systems with other therapeutic modalities, such as chemotherapy and radiotherapy, has demonstrated enhanced anti-tumor effects. Overall, the engineering and targeting of neutrophils for cancer therapy offer a promising avenue for improving treatment outcomes and reducing side effects.