Tuberculosis is the most deadly infectious disease. In particular, pulmonary tuberculosis, being the predominant one, is highly contagious. In past the 200 years, one billion tuberculosis (TB) deaths had occurred, and it is anticipated that in the next 25 years, more than 40 million people may be killed by TB unless control measures are implemented. There are various causes which increase the susceptibility to Mycobacterium tuberculosis infection; these include weakened immune system which occurs through various diseases and medications like human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), type II diabetes, end-stage kidney disease, alcoholism and intravenous drug use, certain cancers, cancer treatment such as chemotherapy, malnutrition and very young or advanced age. Some other factors include tobacco use, which increases the risk of getting TB and dying from it. In this manuscript, the authors tried to summarize all the alterations occurring in immune system at cellular and molecular level which occur due to infection, metabolic changes and chemical exposure, which increase susceptibility to mycobacterial infection.