Understanding the biological process involving metals and biomolecules in the brain is essential for establishing the origin of neurological disorders, such as neurodegenerative and psychiatric diseases. From this perspective, this critical review presents recent advances in this topic, showing possible mechanisms involving the disruption of metal homeostasis and the pathogenesis of neurological disorders. We also discuss the main challenges observed in metallomics studies associated with neurological disorders, including those related to sample preparation and analyte quantification.