Methadone maintenance treatment (MMT) has been scaled up significantly in recent years. This study aimed to investigate the pattern of polysubstance use in 395 MMT patients and its contextualized associated factors. A cross-sectional study was performed in three outpatient MMT clinics in Nam Dinh Province. Multivariate Poisson regression was used to identify factors associated with polysubstance use status. The mean MMT duration and the current MMT dose was 3.3 years and 69.2 mg, respectively. Among participants, 24.8% reported daily alcohol use, 68.6% smoked regularly, and 6% used illicit drugs. Peer pressure and MMT suboptimal adherence were found to associate with continual usage of drugs (47.8%). Participants who lived with a spouse/partner, were self-employed, and smoked were more likely to drink alcohol. Those who drink were also more likely to smoke, and vice versa. Recommendations for policymakers include community-based education and promotional programs aiming to decrease substance usage in the community as well as encouraging and supporting the private health sector in establishing private MMT services and clinics. Further longitudinal studies on polysubstance usage among MMT patients should also be conducted.