This study assessed institutional performance and inter-agency coordination in Substance Use Disorder (SUD) prevention in Nigeria. The aim was to evaluate the performance and coordination of institutions responsible for SUD prevention and to determine whether coordination significantly influences institutional performance. A cross-sectional survey design was employed. A sample of 400 participants was chosen from legal experts, law enforcement agencies including the National Drug Law Enforcement Agency (NDLEA) and the Nigeria Police Force, Non-Governmental Organizations (NGOs), Civil Society Organizations (CSOs), and People Who Use Drugs (PWUD). The respondents were drawn from four states – Bayelsa, Lagos, Kaduna, and Enugu, representing four geopolitical zones in Nigeria. The data were analyzed using frequencies and percentages, cross-tabulations, ANOVA, and Kruskal–Wallis tests to explore inter-agency differences. An ordered logistic regression model was utilized to evaluate the impact of coordination on performance, incorporating cluster-robust standard errors. Additionally, a multilevel ordered logistic regression was performed as a robustness check to address the nesting of data within agencies. Findings showed that institutional performance in SUD prevention was generally rated as moderate to good, with law enforcement agencies and NGOs viewed as performing significantly better than other stakeholder groups. Coordination was also found to be rated as moderate (fair to good) but varied significantly across different agencies, with perceptions being less favourable among people who use drugs. The findings as well showed that higher levels of coordination significantly increased the likelihood of improved institutional performance, even after controlling for capacity, funding, and agency type. The study concluded that strengthening inter-agency coordination is critical to improving SUD prevention outcomes in Nigeria. Policy efforts should prioritize institutionalized coordination platforms and capacity enhancement to improve efficiency, reduce duplication, and maximize public health impact.