Cancer metabolism has long been interpreted through Otto Warburg’s original observation that malignant cells favor aerobic glycolysis due to defective mitochondria. Although foundational, this view is now recognized as incomplete. Contemporary evidence demonstrates that mitochondria in cancer cells remain highly functional and play indispensable roles far beyond adenosine triphosphate (ATP) production. Many tumors actively engage mitochondrial oxidative phosphorylation (OXPHOS) alongside glycolysis, enabling metabolic flexibility across the heterogeneous tumor microenvironment (TME). Mitochondria also generate reactive oxygen species (ROS) that stabilize hypoxia-inducible factor-1 (HIF-1), reinforcing pathways that promote angiogenesis, invasion, and survival under hypoxic stress. Beyond bioenergetics and redox regulation, mitochondria critically shape cancer progression through calcium homeostasis and dynamic remodeling. Meanwhile, mitochondrial fusion and fission govern organelle quality control and functional redistribution. Fusion sustains OXPHOS and cancer stem cell quiescence, whereas fission promotes proliferation, migration, immune evasion, and therapy resistance. Collectively, these findings establish mitochondria as central regulators of tumor evolution, influencing survival in the TME, immune escape, malignant upgrading, and resistance to chemotherapy, radiotherapy, and immunotherapy. Understanding mitochondrial biology, therefore, provides essential insight into cancer progression and reveals promising therapeutic opportunities.