Tuberculosis (TB), despite anti-mycobacterial therapies and vaccine, is a deadly infectious disease with about 12 million incident cases worldwide. Existing Bacillus Calmette-Guérin (BCG) vaccine is unquestionably inexpensive, safe and effective against severe forms of childhood TB but appears to be limited in effectiveness against adult pulmonary disease in endemic areas. Genetic variation in the population is the major obstruction inhibiting validation of biomarkers for protective human immunity against TB. Since current TB cases are presenting new challenges with threats of HIV co-infection therefore various attempts at a global platform are being made to develop a new modified vaccine against it. Consequently, Modified Vaccinia Ankara virus (MVA) vectored MPT64 & Ag85A delivery and polyvalent DNA vaccine, expressing an ESAT6–Ag85B fusion protein etc. are preclinically tested for boosted immune effects. However, better vaccine approaches still need to be developed against M. tuberculosis which can be unbeaten in most infected areas