Abstract: Mitochondria, as the central hub regulating cellular metabolism and apoptosis, exhibit dynamic networks (fusion/fission, autophagy) whose dysregulation is closely linked to the pathogenesis of cancer, neurodegenerative diseases, and metabolic disorders. Conventional drug delivery systems fail to overcome the challenges of lysosomal escape and transmembrane delivery, resulting in systemic toxicity and targeting failures that severely limit clinical applicability. Recent mitochondrial-targeting strategies have achieved breakthroughs through an innovative tripartite framework—"precision delivery, dynamic responsiveness, and synergistic therapy" significantly enhancing delivery efficiency and therapeutic precision. However, heterogeneity in membrane potential, unclear mechanisms of carrier-biointerface interactions, and challenges in manufacturing scalability remain major bottlenecks for clinical translation. Future efforts must integrate pharmaceutics, synthetic biology, and computational materials science to develop closed-loop feedback-based intelligent carriers and establish standardized preclinical evaluation systems, thereby accelerating the implementation of precision medicine.