This study investigated the characteristics and outcomes of drug-resistant tuberculosis patients in selected rural healthcare facilities in the Eastern Cape, South Africa. A retrospective review of clinical records from 456 patients, covering the period from January 2018 to December 2020, revealed a statistically significant relationship between DR-TB types and age groups (Chi-square statistic: 30.74, p-value: 0.015). Younger adults (19–35 years) and middle-aged adults (36–50 years) are more frequently affected by RR-TB and MDR-TB, which are the most prevalent forms of DR-TB. Less common types, including Pre-XDR, XDR, and INH TB, were observed in smaller numbers. The study suggests that DR-TB imposes a heavy burden on the working age population. Gender analysis shows that while the frequency of DR-TB differs between males and females, the percentage distribution of DR-TB types is relatively equal. Both genders are predominantly affected by RR-TB and MDR-TB, which together account for nearly 90% of cases. Pre-XDR, XDR, and INH-resistant TB are much less common, comprising only a small percentage of cases in both males and females. High-risk behaviors such as smoking and drinking are linked to a wider diversity of DR-TB types, while occupations like mining and prison work show higher rates of RR-TB and MDR-TB. In HIV-positive individuals, DR-TB is more common, but the distribution of DR-TB types between HIV-positive and negative groups shows no statistically significant difference. However, HIV-positive individuals have a 20% lower survival rate (65%) compared to HIV-negative patients (85%). Financial stability and comorbidities also significantly influence outcomes, with patients having stable income and fewer high-risk comorbidities experiencing better survival and treatment outcomes. The findings underscore the importance of addressing socioeconomic disparities and strengthening healthcare infrastructure to improve DR-TB treatment outcomes in rural Eastern Cape.