Tuberculosis (TB) remains one of the most alarming global health problems and is a contagious bacterial infection caused by Mycobacterium tuberculosis. It has become increasingly challenging to treat because of drug resistance, which may be due to prolonged drug exposure, poor patient adherence, drug efflux, impermeability of the cell envelope, and others. Therefore, the development of new drugs/formulations against drug-resistant forms of TB is a significant therapeutic challenge. During the last decade, researchers have focused on the exploration of new drugs/repurposing drugs, novel drug delivery systems like nanotechnology-based therapies, and new treatment regimens to fight against the drug-resistant treatment of TB. A nano-drug-based targeted and precise drug delivery system could improve therapeutic efficacy and reduce the adverse effects of treating resistant TB by improving the physicochemical and biological properties of drugs. However, the clinical translation of nanomaterials faces challenges toward safety and efficacy. In conclusion, nanotechnology-based drug repurposing represents a promising and innovative therapeutic approach for TB. It leverages the advantages of existing pharmacological agents while addressing their limitations through precision delivery systems. As research continues to advance, this integrated strategy holds the potential to revolutionize TB treatment, reduce disease burden, and curb the spread of drug-resistant TB worldwide.