Lipid metabolism is important for processes, such as tumor progression, because cancer cells undergo metabolic changes that assist in maintaining their growth, survival, and metastasis. During the development, cancer cells usually adapt to several changes in the tumor microenvironment (TME) and immune modulation. In tumor progression, overexpression of enzymes such as fatty acid (FA) synthase and other related oncogenes in de novo lipid biosynthesis occurs, thus promoting angiogenesis and related growth factors. In recent research, the role of sphingosine-1-phosphate, which activates inflammatory signaling molecules, has been explored in depth. Subsequently, abnormal cholesterol homeostasis, oxidation of FAs, and phospholipid (PL) metabolism might provoke cancer metastasis and tumor evasion. Thus, lipid metabolism has an important role in cancer biology in promoting tumor progression. Consequently, by understanding these molecular mechanisms of lipid biosynthesis in cancer development and progression, it might help to discover novel therapeutic strategies for treating several types of cancers and alleviate immunotherapy-resistant tumors and chemoresistance. This chapter deals with a comprehensive overview of lipid metabolic pathways, response to oxidative stress, and their contribution toward the formation of tumor cells and oncogenesis.