Substance use disorders (SUD) and HIV-associated neurocognitive disorders (HAND) work synergistically as a significant cause of cognitive decline in adults and adolescents globally. Current therapies continue to be limited due to difficulties crossing the blood-brain barrier (BBB) leading to limited precision and effectiveness, neurotoxicity, and lack of co-treatment options for both HAND and SUD. Nanoparticle-based therapeutics have several advantages over conventional therapies including more precise targeting, the ability to cross the BBB, and high biocompatibility which decreases toxicity and optimizes sustainability. These advantages extend to other neurological disorders such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). This review summarizes recent advances in nanotechnology for application to HAND, SUD, and co-treatment, as well as other neurological disorders. This review also highlights the potential challenges these therapies face in clinical translation and long-term safety.