Background: Mycobacterium tuberculosis, the etiology of pulmonary and extra pulmonary tuberculosis is taunted to have predated the existence of mankind, and science has elucidated its presence in old Egyptian' mummies, as it continues to evade current antibiotic treatments, wreck the havoc and decimate human populations. Presented here, are the Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis of Mycobacterium tuberculosis, and the first proposal for the application of this innovative concept in the field of Tuberculosis research, to proffer holistic platform, focused knowledge, and strategies at undermining the prowess of the tubercle bacilli and overcoming its scourge. Materials and Methods: A systematic review was carried out to mine data on the strengths, the weaknesses, the opportunities and threats to M. tb, by review of several publications using meaningful theme and specific search phrases on the subject. Results: Strengths of Mycobacterium tuberculosis include: possession of abundant cell wall mycothiol; M. tb is highly contagious and requires low infectious dose (ID50) to establish infection; ability to specifically target and replicate in the host' macrophages; ability to establish extrapulmonary multiorgan involvement; dual polymorphism i.e. existence in both an actively replicating form as well as or latent state; assumption of variable metabolic states; delayed seeding from the lungs of the replicating bacteria cells to the mediastinal lymph nodes; delayed macrophage apoptosis prior to bacterial growth and ultimate cellular necrosis; ability to shift to glyoxylate pathway during lipid metabolism in lieu of glucose during persistence phase in the host. Weaknesses of M. tuberculosis include: the requirement for growth of a membrane protein called Rv3671c during in vivo replication for survival in the acidic milieu of the macrophages and phagosome; M. tb is a fastidious slow growing bacterium with long generation time; establishment of productive infection in less than 10% of infected subjects; the bacterium is strictly an intracellular aerobic pathogen; and variable M. O. Babalola 185 bacteria level of adenosine triphosphate. Opportunities harnessed by M. tb include: development and spread of resistant strains owing to inadequate and inappropriate drug treatment; limited efficacy and use of BCG Vaccine; MDR-TB is under-diagnosed in children; pathogenic synergy of coinfection of the Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (MTB); difficulty of TB screening in HIV-infected persons; immune status of the host; immigration; slow response of the cellular immune response to M. tb which enables constant endogenous reinfection of the host; anatomical vulnerability of the lungs; aerosols by inspired air is crucial for latent tuberculosis infection. Threats to M. tuberculosis include: the development and use of sensitive combination of microbiological tests as the gold-standard in HIV infected patients; annual TB test; selective isolation of TB patients by reintroduction o...