Eicosanoids, including prostaglandins and leukotrienes, are biologically active lipids involved in inflammation and cancer. This review highlights their roles in epithelial-derived tumors and their microenvironment. Genetic mutations, chronic inflammation, diet, and lifestyle are risk factors for cancer. High-fat diets are linked to increased cancer risk, particularly in colorectal, breast, pancreatic, and prostate cancers. Arachidonic acid metabolism via COX, LOX, and P450 pathways generates eicosanoids, which contribute to cancer progression. NSAIDs reduce cancer risk by inhibiting COX activity, but their use is limited by side effects. COX2 is upregulated in many cancers, while 5-LOX has procarcinogenic roles. Prostanoids and leukotrienes influence tumor growth, survival, migration, and the tumor microenvironment through various signaling pathways. Prostaglandins and leukotrienes regulate stem cell homeostasis and are key mediators in tumor-stromal interactions. Pro-inflammatory prostaglandins and leukotrienes promote tumor growth by regulating epithelial cells and the tumor microenvironment. Prostaglandins and leukotrienes modulate tumor cell proliferation, apoptosis, and migration. They are central to stem cell regulation and tumor microenvironment adaptation. NSAIDs are still promising chemopreventive agents, but their side effects limit their use. Understanding eicosanoid roles in cancer may lead to better chemopreventive and therapeutic agents. Prostanoids and leukotrienes are key in tumor progression and chronic inflammation. Prostaglandins and leukotrienes influence tumor growth, angiogenesis, and immunosuppression. Leukotrienes are potent inflammatory mediators involved in carcinogenesis. Prostaglandins and leukotrienes modulate tumor cell proliferation, differentiation, and apoptosis. They also affect tumor cell migration and invasion. Prostaglandins and leukotrienes regulate stem cell homeostasis and tumor microenvironment. Chronic inflammation promotes tumor growth by altering eicosanoid metabolism. Prostaglandins and leukotrienes mediate crosstalk between tumor cells and stromal cells. Prostaglandins and leukotrienes contribute to tumor immunosuppression by inhibiting immune cell function. Angiogenesis is crucial for tumor growth and metastasis, with prostaglandins and leukotrienes modulating angiogenic factors. Therapeutic agents targeting eicosanoid pathways, such as COX2 and 5-LOX inhibitors, show promise in cancer prevention and treatment. Personalized cancer prevention and treatment approaches may benefit from understanding eicosanoid roles in individual cancers. Eicosanoids like PGE2, LTB4, and LTD4 promote tumor growth, while PGD2 suppresses it. Targeting eicosanoid receptors and pathways may lead to more effective and safer cancer therapiesEicosanoids, including prostaglandins and leukotrienes, are biologically active lipids involved in inflammation and cancer. This review highlights their roles in epithelial-derived tumors and their microenvironment. Genetic mutations, chronic inflammation, diet, and lifestyle are risk factors for cancer. High-fat diets are linked to increased cancer risk, particularly in colorectal, breast, pancreatic, and prostate cancers. Arachidonic acid metabolism via COX, LOX, and P450 pathways generates eicosanoids, which contribute to cancer progression. NSAIDs reduce cancer risk by inhibiting COX activity, but their use is limited by side effects. COX2 is upregulated in many cancers, while 5-LOX has procarcinogenic roles. Prostanoids and leukotrienes influence tumor growth, survival, migration, and the tumor microenvironment through various signaling pathways. Prostaglandins and leukotrienes regulate stem cell homeostasis and are key mediators in tumor-stromal interactions. Pro-inflammatory prostaglandins and leukotrienes promote tumor growth by regulating epithelial cells and the tumor microenvironment. Prostaglandins and leukotrienes modulate tumor cell proliferation, apoptosis, and migration. They are central to stem cell regulation and tumor microenvironment adaptation. NSAIDs are still promising chemopreventive agents, but their side effects limit their use. Understanding eicosanoid roles in cancer may lead to better chemopreventive and therapeutic agents. Prostanoids and leukotrienes are key in tumor progression and chronic inflammation. Prostaglandins and leukotrienes influence tumor growth, angiogenesis, and immunosuppression. Leukotrienes are potent inflammatory mediators involved in carcinogenesis. Prostaglandins and leukotrienes modulate tumor cell proliferation, differentiation, and apoptosis. They also affect tumor cell migration and invasion. Prostaglandins and leukotrienes regulate stem cell homeostasis and tumor microenvironment. Chronic inflammation promotes tumor growth by altering eicosanoid metabolism. Prostaglandins and leukotrienes mediate crosstalk between tumor cells and stromal cells. Prostaglandins and leukotrienes contribute to tumor immunosuppression by inhibiting immune cell function. Angiogenesis is crucial for tumor growth and metastasis, with prostaglandins and leukotrienes modulating angiogenic factors. Therapeutic agents targeting eicosanoid pathways, such as COX2 and 5-LOX inhibitors, show promise in cancer prevention and treatment. Personalized cancer prevention and treatment approaches may benefit from understanding eicosanoid roles in individual cancers. Eicosanoids like PGE2, LTB4, and LTD4 promote tumor growth, while PGD2 suppresses it. Targeting eicosanoid receptors and pathways may lead to more effective and safer cancer therapies