Copper plays a crucial role in a variety of cellular processes, such as energy metabolism, mitochondrial respiration, and antioxidation. Intracellular copper homeostasis relies on the dynamic balance among copper intake, storage, and efflux. Disruptions in copper metabolism can impact cellular function and viability. Elevated copper levels have been observed in various neurodegenerative diseases and tumors, with the underlying pathological mechanisms closely associated with cuproptosis induced by copper overload. This article provides in-depth insights into intracellular copper homeostasis and its maintenance, as well as the roles and molecular mechanisms of copper metabolic disorders and cuproptosis in neurodegenerative diseases and tumorigenesis.