 Geographical hotspots with high frequency of multi-drug-resistant tuberculosis, MDRTB, have been observed in several locations, such as the country of Georgia. Here, the authors analyzed genomic sequences from tuberculosis bacteria isolated from Georgia to show that the transmission fitness of MDRTB strains is heterogeneous, and highly drug-resistant and transmissible isolates contribute to the emergence and maintenance of MDRTB hotspots. This article was authored by Chloe Loisot, Ethel M. Windels, Sebastian M. Jiggly, and others.