Mycobacterium tuberculosis is responsible for Tuberculosis disease in human which possess major challenge to health care system. This is due to complex architecture of this pathogen which enables to thrive and encounter hostile micromilieu which is customized to kill the pathogen. The mycobacterial cell envelope is enriched with lipoglycans like lipoarabinomannan (LAM) which orchestrate the interaction of pathogen with host cell. LAM is structurally diverse and displayed on membrane as mannose-capped LAM (ManLAM) and phosphatidylinositol LAM (PI-LAM). Each of these is endowed with different immunomodulatory activities in host. ManLAM inhibits pro-inflammatory programming by tweaking the production of IL-10, inhibiting the budding of phagosomes into lysosomes and favours persistence of the bacteria. In contrast, PI-LAM triggers pro-inflammatory response and augment autophagy in host. LAM offer intrinsic resistance in pathogen toward oxidative stress, ferroptosis and cathepsin-dependent phagosome maturation. LAM-directed IL-10–producing B cells contribute to the virulence and therapeutic challenge. In view of above, LAM is therefore a distinctive target for mitigating mycobacterial "yardstick" of pathogenesis and drug resistance. Developing LAM based approach may offer impactful outcome not only in prognosis and also developing effective host-directed therapy strategies.