Eicosanoids, including prostaglandins and leukotrienes, are biologically active lipids that play crucial roles in various pathological processes, such as inflammation and cancer. This review highlights the intricate roles of eicosanoids in epithelial-derived tumors and their microenvironment. The metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (LOX) pathways generates eicosanoids, which are involved in governing tumor epithelial cell proliferation, survival, and migration, as well as adapting the tumor microenvironment by influencing angiogenesis, inflammation, and immunosuppression. Prostaglandins, such as PGE2, promote tumor growth through multiple signaling pathways, while leukotrienes, particularly LTB4 and LTD4, also contribute to carcinogenesis. The role of eicosanoids in cancer progression can be understood through their effects on tumor epithelial cells and the inflammatory microenvironment. Therapeutic and chemopreventive agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and specific receptor antagonists, have shown promise in reducing cancer risk and improving outcomes. Understanding the molecular mechanisms underlying the role of eicosanoids in cancer progression will help develop more effective chemopreventive and therapeutic agents.Eicosanoids, including prostaglandins and leukotrienes, are biologically active lipids that play crucial roles in various pathological processes, such as inflammation and cancer. This review highlights the intricate roles of eicosanoids in epithelial-derived tumors and their microenvironment. The metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (LOX) pathways generates eicosanoids, which are involved in governing tumor epithelial cell proliferation, survival, and migration, as well as adapting the tumor microenvironment by influencing angiogenesis, inflammation, and immunosuppression. Prostaglandins, such as PGE2, promote tumor growth through multiple signaling pathways, while leukotrienes, particularly LTB4 and LTD4, also contribute to carcinogenesis. The role of eicosanoids in cancer progression can be understood through their effects on tumor epithelial cells and the inflammatory microenvironment. Therapeutic and chemopreventive agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and specific receptor antagonists, have shown promise in reducing cancer risk and improving outcomes. Understanding the molecular mechanisms underlying the role of eicosanoids in cancer progression will help develop more effective chemopreventive and therapeutic agents.