Cancer cells rewire their metabolism to sustain ATP and macromolecule production, with a particular focus on altered fatty acid (FA) metabolism. This review examines four main areas of research: (1) de novo synthesis and exogenous uptake of FAs, (2) molecular heterogeneity and oncogenic signal transduction pathways regulating FA metabolism, (3) the role of FAs in cancer progression and metastasis, and (4) therapeutic strategies targeting FA metabolism. FAs are crucial for membrane structure, signaling, and energy production. Cancer cells rely on both de novo lipogenesis and exogenous FA uptake, facilitated by specialized transporters like CD36. Exogenous FA uptake allows cancer cells to adapt to metabolic stress, while de novo lipogenesis synthesizes a diverse range of FAs. Oncogenic signaling pathways, such as PI3K-AKT-mTOR, regulate FA metabolism, influencing lipid synthesis and β-oxidation. The complex interplay between oncogenic signaling and dysregulated FA metabolism holds promise for uncovering metabolic vulnerabilities and improving targeted therapies.Cancer cells rewire their metabolism to sustain ATP and macromolecule production, with a particular focus on altered fatty acid (FA) metabolism. This review examines four main areas of research: (1) de novo synthesis and exogenous uptake of FAs, (2) molecular heterogeneity and oncogenic signal transduction pathways regulating FA metabolism, (3) the role of FAs in cancer progression and metastasis, and (4) therapeutic strategies targeting FA metabolism. FAs are crucial for membrane structure, signaling, and energy production. Cancer cells rely on both de novo lipogenesis and exogenous FA uptake, facilitated by specialized transporters like CD36. Exogenous FA uptake allows cancer cells to adapt to metabolic stress, while de novo lipogenesis synthesizes a diverse range of FAs. Oncogenic signaling pathways, such as PI3K-AKT-mTOR, regulate FA metabolism, influencing lipid synthesis and β-oxidation. The complex interplay between oncogenic signaling and dysregulated FA metabolism holds promise for uncovering metabolic vulnerabilities and improving targeted therapies.