Tuberculosis (TB), humanity’s longest running pandemic, has been the number one global cause of infectious disease mortality for decades. Sixty percent of the world’s TB occurs in Asia, where multiple co-morbidities are prevalent in the most vulnerable populations. To accelerate TB elimination, a shift in public health strategies is required which needs to be informed by understanding transmission dynamics, host susceptibility, pathogen virulence and resistance determinants. We answer these fundamental knowledge gaps using a genomics approach to drive translation of genomic discoveries for improved TB control and treatment outcomes. Here I will describe our research on the co-expansion of humans and the ancient bacteria Mycobacterium tuberculosis across Asia, the human genetic susceptibility to TB using GWAS in Vietnam and East Asia, the genomic epidemiology of TB transmission in Nepal, and how the evolution of M.tuberculosis impacts virulence and drug resistance.