Neutrophils are the body’s first responders to injury or infection. They have an unparalleled ability to migrate toward gradients of chemoattractants, which are released at sites of inflammation, and to clear pathogens or cell debris by using a plethora of functions including phagocytosis, the release of cytotoxic enzymes or reactive oxygen species (ROS), and the release of neutrophil extracellular traps (NETs) (1). In addition, neutrophils have been reported in the tumor microenvironment (TME) (2), which has been described as a site of persistent inflammation similar to “wounds that do not heal” (3). The TME harbors a wide variety of diffusible mediators released from both tumor and stromal cells. These mediators induce neutrophil migration toward tumors and alter neutrophil function to promote or limit cancer progression. While studies have focused on understanding the tumor promoting or impairing properties of neutrophils, many questions remain unanswered about the identity of the mediators that control neutrophil recruitment to tumor sites and the function of tumor-associated neutrophils, referred to as TANs. In this perspective, we present an overview of the functions of TANs and the different classes of mediators that have been linked to neutrophil recruitment to tumors, discuss how cancer-associated changes such as the epithelial to mesenchymal transition (EMT) upregulate the expression of the mediators, and review the secretory mechanisms that potentially underlie the release of the mediators in the TME. Finally, we discuss our current understanding of the crosstalk between mediators, with a special focus on TGF-β and chemokines, to provide insights into the integrated mechanisms underlying neutrophil recruitment to the tumor niche and suggest gaps in knowledge that need to be filled for the development of anti-cancer therapeutic interventions.