Electronic cigarettes (e-cigarettes) have achieved global adoption, with an estimated 82 million users worldwide and disproportionate uptake among adolescents. Despite marketing as a safer tobacco alternative, e-cigarette aerosols contain neurotoxic constituents including nicotine, flavoring agents, carbonyl compounds, and heavy metals. This review maps empirical evidence on CNS effects of e-cigarette exposure across biological model types. A systematic scoping review was conducted per the Arksey and O'Malley framework and reported per PRISMA-ScR guidelines. PubMed and Scopus were searched in January 2026 for studies from 2015 to 2026 examining quantifiable CNS outcomes following e-cigarette exposure in human, animal, or in vitro models. Data were extracted across eight domains and synthesized narratively. Seventy-four studies met inclusion criteria: 49 animal in vivo (66.2%), 17 human (23.0%), and 8 in vitro (10.8%), spanning 14 countries. Seven CNS outcome domains were identified: neuroinflammation and oxidative stress, blood-brain barrier (BBB) integrity, cognitive and behavioral outcomes, neuroimaging and pharmacokinetics, neurotransmitter systems and electrophysiology, developmental neurotoxicology, and other outcomes. Neuroinflammation and BBB disruption showed high directional consistency. Cognitive impairment, hippocampal volume reductions, and reward circuit reorganization were consistently observed. Developmental studies identified epigenomic reprogramming and disrupted GABAergic interneuron migration. Non-nicotine constituents were independently implicated in CNS toxicity. E-cigarette exposure is associated with a consistent and biologically plausible pattern of CNS harm. The developing brain represents a priority risk population. Current evidence does not support the neurological safety of e-cigarettes; regulatory frameworks should mandate CNS-specific toxicity assessment for electronic nicotine delivery systems.