Here, this review emphasizes the pleiotropic roles of adipocyte secretome in remodeling breast cancer progression, including representative cytokines (IL-6, IL-8, and chemokines), adipokines (leptin, adiponectin, autotaxin, and resistin), lipid metabolites (free fatty acids and β-hydroxybutyrate), and other exosome-encapsulated substances, as well as their performance in vicious tumor-adipose interaction, immune regulation, and breast cancer diagnosis breast cancer therapy. This evidence concerns the gene ENPP2 and neoplasm.