Tuberculosis (TB) remains a major global health challenge, and adherence to anti-tuberculosis treatment is essential for treatment success and prevention of treatment interruption and drug resistance. Adherence is influenced by interacting individual, social, economic, treatment-related, and health-system conditions. This systematic review aimed to identify and synthesize evidence published between 2021 and 2026 regarding factors influencing adherence to TB treatment, with particular attention to socioeconomic, health-system, patient-related, social, stigma-related, and technology-related determinants. A PRISMA-guided systematic review searched PubMed, Scopus, and Web of Science for studies published from January 2021 to August 2026. Of 72 articles identified, 8 eligible quantitative, qualitative, or mixed-methods studies were included to synthesize barriers and facilitators of tuberculosis (TB) treatment adherence using a multidimensional framework. Twenty-four studies were reported as meeting the inclusion criteria, comprising 10 cross-sectional studies, 6 cohort studies, 5 qualitative studies, and 3 randomized trials. Five major domains emerged: socioeconomic factors; health-system factors; patient-related factors; social support and stigma; and technology-based adherence approaches. Reported barriers included poverty, transportation costs, food insecurity, prolonged waiting times, medication stock-outs, poor provider–patient communication, forgetfulness, adverse effects, comorbidities, substance use, and stigma. Family support was repeatedly identified as a facilitator, whereas digital adherence interventions demonstrated heterogeneous effects across settings. TB treatment adherence is multidimensional and requires interventions that address practical access barriers, quality of health services, treatment-related difficulties, social support, and stigma in addition to patient education.