The article reviews the role of mitochondrial metabolism in cancer, highlighting its significance in both cell-intrinsic and cell-extrinsic mechanisms. Mitochondria play a central role in oncogenesis by providing bioenergetic support, anabolic building blocks, controlling redox and calcium homeostasis, regulating transcription, and governing cell death. They are promising targets for novel anticancer agents. However, tumors interact closely with the host immune system, and many immunological functions rely on intact mitochondrial metabolism. The review discusses how mitochondria influence malignant transformation, tumor progression, and response to treatment, emphasizing the therapeutic potential of targeting mitochondrial metabolism. Key mechanisms include the production of reactive oxygen species (ROS), accumulation of oncometabolites, and altered susceptibility to regulated cell death (RCD). Mitochondrial metabolism also impacts tumor progression through proliferation, resistance to RCD, diversification, interaction with the stroma, and metastatic dissemination. Additionally, mitochondria influence immunosurveillance by releasing danger signals and affecting immune cell functions. The article concludes by discussing the challenges and opportunities in developing strategies to specifically modulate mitochondrial functions in cancer therapy.The article reviews the role of mitochondrial metabolism in cancer, highlighting its significance in both cell-intrinsic and cell-extrinsic mechanisms. Mitochondria play a central role in oncogenesis by providing bioenergetic support, anabolic building blocks, controlling redox and calcium homeostasis, regulating transcription, and governing cell death. They are promising targets for novel anticancer agents. However, tumors interact closely with the host immune system, and many immunological functions rely on intact mitochondrial metabolism. The review discusses how mitochondria influence malignant transformation, tumor progression, and response to treatment, emphasizing the therapeutic potential of targeting mitochondrial metabolism. Key mechanisms include the production of reactive oxygen species (ROS), accumulation of oncometabolites, and altered susceptibility to regulated cell death (RCD). Mitochondrial metabolism also impacts tumor progression through proliferation, resistance to RCD, diversification, interaction with the stroma, and metastatic dissemination. Additionally, mitochondria influence immunosurveillance by releasing danger signals and affecting immune cell functions. The article concludes by discussing the challenges and opportunities in developing strategies to specifically modulate mitochondrial functions in cancer therapy.