Introduction. Successful interventions for substance use disorders (SUDs), though obtainable, are not effectively utilized due to the high cost of treatment. The adoption of any given therapy is often impeded by insufficient evidence of the effectiveness of such treatment. Objective. This study aimed to assess the direct medical cost of treating SUD in two tertiary hospitals in South-West, Nigeria. Methods. A descriptive, cross-sectional survey of patients managed for SUD at the two psychiatric hospitals was carried out between January and June 2020. The inclusion criteria were patients with SUD above 18 years of age, registered and managed at the two hospitals. Data were collected from selected patients' case notes using a standardized data collection tool and analyzed using descriptive and inferential statistics. Results. The average costs of treatment for alcohol use disorder, drug use disorder, and drug and alcohol use disorder were ₦146,425.38 ± 57,388.84, ₦135,282.09 ± 53,190.39, and ₦143,877.33 ± 68,662.04, respectively. This translates to $384.82, $355.53, and $378.12, respectively. The highest contributors to SUD treatment cost are inpatient admissions and the cost of medicines; inpatient admissions include accommodation, feeding, and laundry. Conclusion. Considering that over 60% of the Nigerian population lives below the poverty line, the direct cost of SUD treatment is unaffordable to the patients and the health care system, which is grossly underfunded.