Mitochondrial metabolism plays a critical role in cancer development and progression, influencing malignant transformation, tumor growth, and response to therapy. While glycolysis was once considered the primary energy source for cancer cells, recent research highlights the essential role of mitochondria in providing bioenergetic support, redox regulation, and metabolic flexibility. Mitochondria also contribute to tumor anabolism by supplying building blocks for cell growth and by modulating cell death pathways. However, cancer cells must navigate a complex interaction with the host immune system, where mitochondrial metabolism is crucial for immune cell function. Targeting mitochondrial metabolism offers promising therapeutic strategies for cancer treatment. Mitochondrial dysfunction can promote malignant transformation through mechanisms such as increased reactive oxygen species (ROS), accumulation of oncometabolites like fumarate, succinate, and 2-hydroxyglutarate, and resistance to mitochondrial outer membrane permeabilization (MOMP) or mitochondrial permeability transition (MPT). These processes are linked to oncogenic signaling pathways and can lead to genomic instability and tumor progression. Mitochondrial metabolism also influences tumor progression by providing energy and metabolic substrates, producing ROS, and regulating cell death pathways. Cancer cells exhibit metabolic plasticity, adapting to different environmental conditions and utilizing various energy sources such as glycolysis, oxidative phosphorylation (OXPHOS), and fatty acid oxidation. Mitochondrial metabolism is also crucial for immunosurveillance, as immune cells rely on mitochondrial function for their metabolic and signaling activities. Cancer cells can evade immune detection by altering their metabolic profile, which can also impact immune cell function. Targeting mitochondrial metabolism may enhance the effectiveness of immunotherapy by modulating immune cell responses. However, the therapeutic targeting of mitochondrial functions must be carefully balanced to avoid unintended effects on immune cells. Overall, mitochondrial metabolism is a key player in cancer development and progression, and understanding its role in tumor biology provides new avenues for the development of targeted therapies. The complex interplay between mitochondrial metabolism and cancer cell biology highlights the need for further research to fully exploit the therapeutic potential of mitochondrial targeting in cancer treatment.Mitochondrial metabolism plays a critical role in cancer development and progression, influencing malignant transformation, tumor growth, and response to therapy. While glycolysis was once considered the primary energy source for cancer cells, recent research highlights the essential role of mitochondria in providing bioenergetic support, redox regulation, and metabolic flexibility. Mitochondria also contribute to tumor anabolism by supplying building blocks for cell growth and by modulating cell death pathways. However, cancer cells must navigate a complex interaction with the host immune system, where mitochondrial metabolism is crucial for immune cell function. Targeting mitochondrial metabolism offers promising therapeutic strategies for cancer treatment. Mitochondrial dysfunction can promote malignant transformation through mechanisms such as increased reactive oxygen species (ROS), accumulation of oncometabolites like fumarate, succinate, and 2-hydroxyglutarate, and resistance to mitochondrial outer membrane permeabilization (MOMP) or mitochondrial permeability transition (MPT). These processes are linked to oncogenic signaling pathways and can lead to genomic instability and tumor progression. Mitochondrial metabolism also influences tumor progression by providing energy and metabolic substrates, producing ROS, and regulating cell death pathways. Cancer cells exhibit metabolic plasticity, adapting to different environmental conditions and utilizing various energy sources such as glycolysis, oxidative phosphorylation (OXPHOS), and fatty acid oxidation. Mitochondrial metabolism is also crucial for immunosurveillance, as immune cells rely on mitochondrial function for their metabolic and signaling activities. Cancer cells can evade immune detection by altering their metabolic profile, which can also impact immune cell function. Targeting mitochondrial metabolism may enhance the effectiveness of immunotherapy by modulating immune cell responses. However, the therapeutic targeting of mitochondrial functions must be carefully balanced to avoid unintended effects on immune cells. Overall, mitochondrial metabolism is a key player in cancer development and progression, and understanding its role in tumor biology provides new avenues for the development of targeted therapies. The complex interplay between mitochondrial metabolism and cancer cell biology highlights the need for further research to fully exploit the therapeutic potential of mitochondrial targeting in cancer treatment.