The widespread accumulation of microplastics (MPs) and nanoplastics (NPs) in the environment, along with their capacity to adsorb and transport co-contaminants, raises increasing concern regarding potential neurotoxic effects. This review synthesizes recent evidence on the combined neurotoxicity of MPs/NPs with environmental co-contaminants, including heavy metals, phthalates, pharmaceuticals, and flame retardants. These contaminants interact with MPs/NPs to enhance bioavailability, facilitate translocation to neural tissues, and trigger adverse biological responses. Mechanistic pathways—including oxidative stress, disruption of neurotransmitter systems, neuroinflammation, and increased blood–brain barrier permeability—have been examined in various in vivo models, particularly fish and rodents. Notably, recent reports indicate that humans may ingest thousands of MP and NP particles annually, with some studies detecting up to 2,000 particles per gram in biological tissues, including the brain. These findings underscore the urgent need for a comprehensive assessment of the potential neurological risks associated with combined exposure to MPs, NPs, and co-contaminants. The synergistic and additive effects of combined exposures underscore the potential for impairments in cognitive, behavioral, and neurochemical functions. This review integrates cross-species evidence to identify key research gaps, including undefined dose thresholds for combined exposures, limited understanding of particle–contaminant interaction kinetics, and insufficient mapping of brain-region–specific vulnerabilities. This review underscores the need for integrated toxicological assessments and strengthened regulatory strategies to address these environmental threats, with particular attention to pharmacologically relevant neurotoxic mechanisms.