Background <p>Tuberculosis (TB) is a leading global infectious disease, presenting a major public health concern, particularly due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. The severity of cough in TB is a critical symptom with the potential for transmission and clinical monitoring. However, the association between genetic mutations in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) strains and cough severity remains underexplored.</p> Objective <p>This study aims to synthesize the existing literature on genomic distinctions between drug-resistant (DR) and drug-sensitive (DS) strains and investigate how these differences relate to the severity of cough.</p> Methods <p>A comprehensive literature search was conducted across multiple databases, including PubMed, Google Scholar, and Cochrane. Keywords included terms such as "Mycobacterium tuberculosis," "drug-resistant," "genomic variations," and "cough severity." Studies were included if they discussed genetic resistance mechanisms in <i>Mtb</i>, compared genomic features of DR and DS strains, or examined strain-specific associations with cough.</p> Results <p>Genetic mutations conferring resistance were identified in DR strains. Mutations such as katG S315T and rpoB S531L contribute not only to antibiotic resistance but also alter bacterial virulence and host immune responses. Enhanced secretion systems and regulatory genes were found to increase inflammatory responses and stimulate the cough reflex. L2 Beijing lineage showed high mutations and virulence, which have been implicated in cough induction.</p> Conclusion <p>This study suggests a genomic link between DR and <i>Mtb</i> mutations and increased cough severity. Such genetic features may elevate transmission through amplified respiratory symptoms. These findings underscore the need for integrating genomic data into clinical and public health strategies to improve TB management, diagnosis, and transmission control.</p>