Discovering the vaccine candidates for tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is regarded as a prime concern across the globe, as per the World Health Organization (WHO). Current drugs are relatively ineffective or insensitive to the infections caused by Mtb due to the increased resistance identified with the term ‘multidrug-resistant tuberculosis’ (MDR-TB), thereby posing a significant challenge in the treatment, making it a global threat. Hence, it is crucial to develop potent drugs and treatment methods to tackle the causative agent. Bacterial biofilms are multicellular complex structures formed by bacteria as a survival tactic and are identified as one of the crucial factors that hinder the treatment of tuberculosis by causing antibiotic resistance, disrupting the immune system, causing persistence of infection, or damaging the lung tissue, consequently impacting the effectiveness of vaccines. On that account, thoroughly understanding the role of biofilms in pathogenesis and their survival tactics is indispensable in designing impactful medicines to reduce the number of illnesses as well as fatalities caused by this multidrug-resistant pathogen. Therefore, it is worthwhile to analyse the existing research to aid in developing future experimental designs. Although there has been a recent surge in studies related to treatment and drug development on MDR-TB, there is a lack of extensive in vivo studies and clinical trials due to various limitations. This review examines the factors contributing to tuberculosis and drug resistance, particularly emphasising their association with mycobacterial biofilms. The review also synthesises findings from existing studies on therapeutic and antibiofilm strategies, including the latest stem cells and nanotechnology, providing insights to support the development of potential anti-TB therapies, vaccine candidates, and advancements in drug discovery of TB. The paucity of advanced medication systems for MDR-TB poses a necessity in discovering sophisticated targeted drug therapeutics for a directed action and, consequently, a viable inference to save the community from this global threat.