Lipid metabolic reprogramming in cancer cells is a critical aspect of oncogenesis, as lipid metabolism is essential for maintaining membrane homeostasis and normal cellular function. This review highlights the key lipid dysfunctions in tumor development, focusing on the roles of specific lipids in oncogenic signaling, endoplasmic reticulum (ER) stress, and intercellular communication within the tumor microenvironment (TME). Cancer cells exhibit altered lipid metabolism, including increased lipid and cholesterol uptake, enhanced lipogenesis, and cholesterol synthesis, which support their growth and survival. These changes are often associated with increased lipid droplet (LD) content, which is linked to cancer aggressiveness and resistance to chemotherapy. Lipid rafts, which are microdomains enriched in cholesterol and sphingolipids, play a crucial role in cancer cell signaling, including the activation of oncogenic pathways and the regulation of cell survival and death. Disruption of lipid raft integrity can inhibit oncogenic signaling and promote apoptosis. Additionally, lipid alterations can induce ER stress, leading to apoptosis through the unfolded protein response (UPR). The tumor-stroma interaction is mediated by lipids and fatty acids, with cancer cells utilizing lipids from the TME for energy and growth. Prostaglandins and sphingolipids, such as sphingosine-1-phosphate (S1P), are key mediators of this communication, influencing tumor growth, angiogenesis, and immune evasion. Targeting lipid metabolism in cancer cells is a promising therapeutic strategy. Inhibitors of lipogenic enzymes, such as fatty acid synthase (FASN), ATP-citrate lyase (ACLY), and acetyl-CoA carboxylase (ACC), have shown efficacy in preclinical models. Additionally, targeting lipid raft components, such as cholesterol, and inducing ER stress through lipid homeostasis disruption can lead to cancer cell death. Therapies that disrupt lipid metabolism, including the use of statins, cholesterol depleting agents, and inhibitors of cholesterol esterification, are being explored for their potential in cancer treatment. Overall, lipid metabolism is a critical factor in cancer progression, and targeting lipid-related pathways offers new opportunities for therapeutic intervention. Understanding the complex interplay between lipid metabolism and cancer cell biology is essential for developing effective treatments for aggressive cancers.Lipid metabolic reprogramming in cancer cells is a critical aspect of oncogenesis, as lipid metabolism is essential for maintaining membrane homeostasis and normal cellular function. This review highlights the key lipid dysfunctions in tumor development, focusing on the roles of specific lipids in oncogenic signaling, endoplasmic reticulum (ER) stress, and intercellular communication within the tumor microenvironment (TME). Cancer cells exhibit altered lipid metabolism, including increased lipid and cholesterol uptake, enhanced lipogenesis, and cholesterol synthesis, which support their growth and survival. These changes are often associated with increased lipid droplet (LD) content, which is linked to cancer aggressiveness and resistance to chemotherapy. Lipid rafts, which are microdomains enriched in cholesterol and sphingolipids, play a crucial role in cancer cell signaling, including the activation of oncogenic pathways and the regulation of cell survival and death. Disruption of lipid raft integrity can inhibit oncogenic signaling and promote apoptosis. Additionally, lipid alterations can induce ER stress, leading to apoptosis through the unfolded protein response (UPR). The tumor-stroma interaction is mediated by lipids and fatty acids, with cancer cells utilizing lipids from the TME for energy and growth. Prostaglandins and sphingolipids, such as sphingosine-1-phosphate (S1P), are key mediators of this communication, influencing tumor growth, angiogenesis, and immune evasion. Targeting lipid metabolism in cancer cells is a promising therapeutic strategy. Inhibitors of lipogenic enzymes, such as fatty acid synthase (FASN), ATP-citrate lyase (ACLY), and acetyl-CoA carboxylase (ACC), have shown efficacy in preclinical models. Additionally, targeting lipid raft components, such as cholesterol, and inducing ER stress through lipid homeostasis disruption can lead to cancer cell death. Therapies that disrupt lipid metabolism, including the use of statins, cholesterol depleting agents, and inhibitors of cholesterol esterification, are being explored for their potential in cancer treatment. Overall, lipid metabolism is a critical factor in cancer progression, and targeting lipid-related pathways offers new opportunities for therapeutic intervention. Understanding the complex interplay between lipid metabolism and cancer cell biology is essential for developing effective treatments for aggressive cancers.