Tuberculosis (TB) is a contagious disease that is a significant cause of illness worldwide and has been declared one of the top ten causes of mortality across the world. It is well known that bacteria within biofilms exhibit much higher drug resistance than individual cells. Biofilms constitute a significant threat in the clinical environment by acting as reservoirs of multidrug-resistant bacteria. Thus, the formation of biofilms has been postulated to further aid in drug insensitivity and bacterial persistence within host tissues. The rapid increase in drug resistance in Mycobacteria poses a significant challenge to TB eradication and needs to be addressed soon. In this review, we have attempted to frame a general overview of mycobacterial pathogenesis, the role of biofilm formation in enhancing its shelf life, and some natural compounds and nanoparticles as emerging novel therapeutics reported to inhibit biofilm formation in mycobacteria. Therefore, we present some recent advances which might have potential applications in new treatment regimens for Tuberculosis.