This article aims to provide a comprehensive description of the postnatal effects of drug exposure on neonates, including neonatal abstinence syndrome (NAS), and the neonatal advanced practice registered nurse (APRN)'s role in working with this vulnerable and marginalized population. Maternal substance use disorders (SUDs) are a significant epidemic in the United States and are a leading cause of infant admission to the NICU. Substance use disorders carry stigmas for individuals experiencing them. The opioid crisis has played a pivotal role, with opioids being the most used substance during pregnancy. Neonatal abstinence syndrome manifests as a multisystem disorder resulting from chronic exposure to illicit or prescribed substances in utero that are abruptly halted at delivery. Symptoms of NAS vary in severity depending on the substance type and duration of exposure. The neonatal APRN is in a unique position to have a positive impact on the care provided to neonates experiencing NAS and their mothers experiencing SUD.