Particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) is one of the criteria air pollutants that (1) serve as an essential carrier of airborne toxicants arising from combustion-related events including emissions from industries, automobiles, and wildfires and (2) play an important role in transient to long-lasting cognitive dysfunction as well as several other neurological disorders. A systematic review was conducted to address differences in study design and various biochemical and molecular markers employed to elucidate neurological disorders in PM2.5 -exposed humans and animal models. Out of 340,068 scientific publications screened from 7 databases, 312 studies were identified that targeted the relationship between exposure to PM2.5 and cognitive dysfunction. Equivocal evidence was identified from pre-clinical (animal model) and human studies that PM2.5 exposure contributes to dementia, Parkinson disease, multiple sclerosis, stroke, depression, autism spectrum disorder, attention deficit hyperactivity disorder, and neurodevelopment. In addition, there was substantial evidence from human studies that PM2.5 also was associated with Alzheimer's disease, anxiety, neuropathy, and brain tumors. The role of exposome in characterizing neurobehavioral anomalies and opportunities available to leverage the neuroexposome initiative for conducting longitudinal studies is discussed. Our review also provided some areas that warrant consideration, one of which is unraveling the role of microbiome, and the other role of climate change in PM2.5 exposure-induced neurological disorders.