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Tuberculosis (TB) remains a critical global health issue, particularly with the emergence of multidrug-resistant tuberculosis (MDR-TB) and its threat to both public health and healthcare systems. Advances in TB diagnosis, treatment, and molecular markers have facilitated progress in the TB management. However, the prevalence of drug-resistant strains and coinfection with HIV has continued to complicate efforts to achieve global TB control goals. Saudi Arabia (KSA) has made substantial strides in TB control through the National Tuberculosis Control Program (NTCP). The study aims to examine the epidemiological trends of TB, including drugresistant strains, and the impact of HIV coinfection in KSA. It also aims to analyze the effectiveness of diagnostic methods and the role of molecular markers in identifying resistant strains. A retrospective analysis was conducted on TB cases reported from 2015 to 2019 in KSA. Data were collected on TB incidence, drug resistance, HIV co-infection rates, and demographic patterns. The study also analyzed regional disparities and changes in clinical presentation, including the prevalence of unusual symptoms. The study observed a gradual decline in TB incidence from 2015 to 2019, meeting the World Health Organization (WHO) milestones. Drug resistance, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, showed a significant reduction during this period. HIV co-infection remained constant, with no major fluctuations. Regional disparities were notable, with a concentration of cases in Makkah, Riyadh, and Jazan. A demographic shift toward younger populations and a rise in native-to-immigrant TB cases were also identified. The results indicate that KSA’s TB control measures have been effective in reducing TB incidence, including drug-resistant cases. However, HIV co-infection remains a public health concern. Continued vigilance enhanced diagnostic techniques, and more targeted interventions in high-risk regions are essential to achieve the goal of a TB-free world by 2035. [ABSTRACT FROM AUTHOR]