Tuberculosis (TB) is a bacterial disease that remains a global health threat due to the millions of deaths attributed to it each year. The emergence of drug resistance has exacerbated and further increased the challenges in the fight against this illness. Despite the preventive measures using the application of the Bacillus Calmette-Guérin vaccine, the desired immunization outcome is not as high as expected. Conventional TB treatments exhibit serious limitations, such as adverse effects and prolonged duration, leading to a pressing need for alternative and more effective treatment options. Despite significant efforts, it took nearly four decades for diarylquinoline to become the most recently approved medicine for this disease. In addition, various possibilities, such as the usage of medications used for many other conditions (repurposed drugs), have been explored in order to speed up the process of achieving faster outcomes. Natural compounds derived from various sources (microorganisms, plants, and animals) have emerged as potential candidates for combating TB due to their chemical diversity and their unique modes of action. Finally, efforts towards the generation of novel vaccines have received considerable attention. The goal of this paper was to perform an analysis of the current state of treating drug-resistant TB and to evaluate possible approaches to this complicated challenge. Our focus is centered on highlighting new alternatives that can be used to combat resistant strains, which have potentiated the health crisis that TB represents.