Background <p>The persistent spread of tuberculosis (TB), driven by multidrug-resistant TB (MDR-TB), poses a major public health threat in Sub-Saharan Africa (SSA), worsening the region’s already high burden of infectious disease mortality. Despite fragmented evidence, a comprehensive quantitative assessment of MDR-TB patient characteristics that fuel resistance across the continent has been limited. This study aimed to synthesize and quantify the demographic, clinical, socio-economic, and behavioral patient profiles associated with MDR-TB in SSA to inform targeted control strategies.</p> Methods <p>We conducted a systematic review and meta-analysis of observational studies published between January 2000 and November 2025 across five databases (PubMed/MEDLINE, Scopus, Web of Science, AJOL, and Google Scholar). Pooled proportions of demographic, clinical, socio-economic, behavioral, and treatment-related characteristics reported among MDR-TB patients were calculated using a random-effects model, with heterogeneity quantified by the I² statistic.</p> Results <p>Thirty-six studies from 15 African countries, predominantly Ethiopia (36%), involving 10,792 participants and 3,864 MDR-TB cases, were included. The pooled proportion of MDR-TB cases across these heterogenous study populations was 39.0% (95% CI: 29–49; I² = 99.9%). Demographically, males (70%) were disproportionately affected. Key socioeconomic characteristics included being a farmer or day labourer (77%; 95% CI: 53–100) and large family size (&gt;5 members) (55.0%; 95% CI: 48–62). HIV co-infection was reported in 34% of cases. Major behavioral and clinical characteristics included alcohol use disorder (48%) and record of previous TB treatment (63%). A history of direct contact with known TB patients was observed in 49% of the cases. While a lack of BCG vaccination (69%) and consultation with traditional healers (86%) were noted, though these parameters were evaluated in only two studies and cannot be generalized across the wider subcontinent.</p> Conclusion <p>The findings suggest that MDR-TB across the included study population in Sub-Saharan Africa is commonly reported alongside systemic treatment failures, behavioral factors, and socio-economic vulnerabilities. Addressing these challenges requires strengthening directly observed therapy short-course (DOTS) through community engagements, integrating traditional healers into referral systems, and enhancing social support to improve adherence.</p> Clinical trial number <p>Not applicable.</p>