The review discusses the critical role of lipid metabolism in cancer development and progression. It highlights how alterations in lipid metabolism, particularly in lipid droplets (LDs) and cholesterol, contribute to tumor growth and metastasis. The authors review the impact of lipid dysfunctions on intracellular oncogenic signaling, endoplasmic reticulum (ER) stress, and the crosstalk between cancer cells and the tumor microenvironment (TME). They also discuss recent advances in therapeutic strategies targeting lipid-related metabolic pathways in cancer, including the use of inhibitors of lipogenic enzymes, cholesterol synthesis, and lipid raft disruption. The review emphasizes the potential of these approaches to exploit the lipid dependency of cancer cells and achieve therapeutic benefits.The review discusses the critical role of lipid metabolism in cancer development and progression. It highlights how alterations in lipid metabolism, particularly in lipid droplets (LDs) and cholesterol, contribute to tumor growth and metastasis. The authors review the impact of lipid dysfunctions on intracellular oncogenic signaling, endoplasmic reticulum (ER) stress, and the crosstalk between cancer cells and the tumor microenvironment (TME). They also discuss recent advances in therapeutic strategies targeting lipid-related metabolic pathways in cancer, including the use of inhibitors of lipogenic enzymes, cholesterol synthesis, and lipid raft disruption. The review emphasizes the potential of these approaches to exploit the lipid dependency of cancer cells and achieve therapeutic benefits.