This review systematically elucidates the metabolic mechanisms of essential transition metal copper in humans, including absorption, distribution, storage, excretion, and homeostatic regulation. It highlights copper's participation in various biochemical reactions through redox cycling between Cu(I) and Cu(II) ions, thereby maintaining protein structure and function, and discusses the pathological basis of cell injury induced by excess free copper mediated reactive oxygen species (ROS) generation. The review emphasizes the association of copper homeostasis dysregulation with multiple diseases, such as liver disorders, neurodegenerative conditions, cardiovascular diseases, and copper-related genetic diseases. It further explores copper's role in cancer biology, particularly its promotion of tumor initiation, proliferation, angiogenesis, and metastasis via signaling pathways, with a focus on the "copper proliferation"–mediated malignant transformation mechanisms. Additionally, recent advances and clinical potential of copper-targeted anticancer strategies—including copper chelators, ionophores, and complexes—are discussed. Finally, the article addresses current challenges in copper-targeted therapies, such as therapeutic heterogeneity across different cancer types and patient populations, and the incomplete understanding of copper signaling networks. Future perspectives are provided, highlighting precision medicine approaches, combination therapies, and novel drug development, aiming to deepen the understanding of copper-related pathology and foster the development of innovative cancer treatments.