Background <p>Substance Use Disorder represents a complex global public health challenge, yet the effectiveness of treatment centers remains debated due to lack of consensus on standardized international indicators and heterogeneity of treatment modalities. This systematic review aimed to identify and synthesize key international indicators for measuring treatment success, compare effectiveness of different modalities, and assess impact on social reintegration.</p> Methods <p>Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Population, Intervention, Comparison, Outcome frameworks, we conducted systematic searches of PubMed, Scopus, Web of Science, and Cochrane Library. Two reviewers independently screened 4,234 records, extracted data from 28 included studies, and assessed quality using Cochrane Risk of Bias 2 and Newcastle-Ottawa Scale. Heterogeneity was quantified using I-squared and tau-squared statistics.</p> Results <p>Core indicators emerged in three domains: physiological (abstinence, daily functioning), psychological (reduced anxiety/depression, craving reduction), and social (employment, family relations). Medication-Assisted Treatment with methadone and buprenorphine demonstrated consistent effectiveness in reducing substance use and preventing relapse. Psychosocial interventions, particularly Cognitive Behavioral Therapy and Mindfulness-Based Relapse Prevention, significantly enhanced quality of life. Integrated models combining pharmacological and psychosocial approaches outperformed single-modality treatments. However, 78.6% of studies originated from four high-income countries, and only 17.9% reported outcomes beyond 12 months.</p> Conclusions <p>Effective Substance Use Disorder treatment requires integrated models with standardized, multidimensional outcome indicators. Future research must prioritize long-term outcomes and address the substantial evidence gap in low- and middle-income countries.</p> Clinical trial number <p>Not applicable.</p>