Neutrophils are key mediators of the immune response and play essential roles in the development of tumors and immune evasion. Emerging studies indicate that neutrophils also play a critical role in the immunotherapy resistance in cancer. In this review, firstly, we summarize the novel classification and phenotypes of neutrophils and describe the regulatory relationships between neutrophils and tumor metabolism, flora microecology, neuroendocrine and tumor therapy from a new perspective. Secondly, we review the mechanisms by which neutrophils affect drug resistance in tumor immunotherapy from the aspects of the immune microenvironment, tumor antigens, and epigenetics. Finally, we propose several promising strategies for overcoming tumor immunotherapy resistance by targeting neutrophils and provide new research ideas in this area.