Background <p>Neonates born to mothers with substance use disorder may require pharmacological or non-pharmacological treatments for withdrawal symptoms post-birth. This study aims to assess parents’ epidemiologic and socioeconomic factors and their correlation with short neonatal outcomes, such as length of hospital stay and discharge disposition.</p> Methods <p>This case-control study was conducted in hospitals affiliated with Shiraz University of Medical Sciences. Demographic and social data of parents and neonatal outcomes, including hospital stay, Finnegan score, and discharge disposition, were extracted from hospital records. Statistical analysis was performed using SPSS, reporting means, percentages, and frequencies. Independent sample t-tests, ANOVA, and chi-square tests were used to evaluate associations between mothers’ socio-demographic background and clinical status. Negative binomial regression was employed to explore risk factors for length of hospital stay.</p> Results <p>The case group comprised 95 neonates born to mothers with substance use disorder, with 122 healthy neonates as the control group. The incidence of birth from mothers with substance use disorder was 1.4%. The mean maternal age was 32.1 ± 6.5 years. The average Finnegan score among affected neonates was 6.85 ± 1.85. Methadone was the most commonly used substance. While all control group neonates were discharged home, only 57.9% of cases were discharged home. Discharge to social services was more common among unmarried and homeless or tenant mothers. Neonates born to mothers with academic degrees had 1.54 times longer hospital stay.</p> Conclusion <p>This study underscores the intricate relationship between maternal substance abuse, socioeconomic factors, and neonatal health, highlighting the necessity for targeted interventions to support mothers with substance use disorder and their infants.</p>