Positron emission tomography (PET) as an advanced noninvasive imaging technique, provides unprecedented insights into the study of physiological and biochemical processes in vivo. Copper-64 (Cu) has a ideal half-life of 12.7 hours, with β+ and β-dual decay modes and abundant coordination chemistry, enabling the development of a wide variety of radiopharmaceuticals for PET imaging and radionuclide therapy.This review provides a comprehensive overview of the latest advances in Copper-64 (Cu)-based PET radionuclides, covering their production, radiolabeling strategies, and clinical applications. It highlights the role of Cu-PET in enhancing diagnostic accuracy and therapeutic outcomes across various tumor types. Additionally, future research directions and the evolving clinical applications of Cu-based radiopharmaceuticals are discussed, offering insights into their potential impact on clinical practice.