Tumor cells undergo metabolic reprogramming to adapt to rapid proliferation and harsh microenvironments, as evidenced by aerobic glycolysis. Mitochondria serve as key coordinators of this process. Under internal and environmental stress in tumors, mitochondria reprogram metabolism by balancing energy dynamics, redirecting metabolic routes, communicating via metabolites, and preserving the quality of mitochondria, thus supporting tumor cell survival. Traditional Chinese medicine (TCM) has a key role in modulating mitochondrial reprogramming in tumor cells, possibly disrupting metabolic pathways that are necessary for survival and proliferation. However, the underlying molecular signaling and cellular biological mechanisms need to be elucidated. In this review, we focused on the Key functions of mitochondria in adapting to tumor metabolic reprogramming are the focus of this review and recent advances in and regulatory mechanisms of TCM and nano-pharmaceutical formulations in maintaining mitochondrial homeostasis are discussed. These insights may help understand the role of mitochondria in the pathogenesis of metabolic diseases, such as cancer, and identify therapeutic targets.