Neutrophils have emerged as important players in the tumor microenvironment, largely attributed to their plasticity and heterogeneity. Evidence accumulated thus far indicates that neutrophils signaled by external cues can promote tumor progression via several mechanisms. Hence, in our quest to target tumor-associated neutrophils to improve treatment, understanding the mechanisms by which tumor-derived factors regulate neutrophils to gain pro-tumor functions and the feedback loop by which these neutrophils promote tumor progression is very crucial. Herein, we review the published data on how tumor-derived factors alter neutrophils phenotype to promote tumor progression with particular emphasis on immunosuppression, autophagy, angiogenesis, tumor proliferation, metastasis, and therapeutic resistance. These deeper insights could provide a wider view and novel therapeutic approach to neutrophil-targeted therapy in cancer.