The application of advanced drug discovery approaches in the fight against tuberculosis (TB) has significantly accelerated the identification and development of novel therapeutics. This review explores various contemporary strategies, including high-throughput screening, structure-based drug design, and computational modelling, that have been employed to discover new anti-TB drugs. Emphasis is placed on the integration of omics technologies, such as genomics, proteomics, and metabolomics, which provide comprehensive insights into Mycobacterium tuberculosis biology and pathogenesis. Additionally, the role of drug repurposing and combination therapy in enhancing treatment efficacy and overcoming drug resistance is discussed. This multifaceted approach aims to address the urgent need for effective TB therapies in the face of rising multidrug-resistant TB strains.