Asthma presents substantial global variability in treatment response, much of which remains unexplained by conventional clinical and biomarker-based assessment. Pharmacogenomics offers a promising avenue for understanding this heterogeneity; however, its translation into routine practice has been slow. This review synthesizes current evidence up to 2025 on key pharmacogenomic markers involved in responses to inhaled corticosteroids, beta-agonists, leukotriene modifiers, and biologics. A structured methodology incorporating risk-of-bias assessment, quantitative and narrative evidence synthesis, and GRADE evaluation was applied. Among available markers, GLCCI1 and CRHR1 show the most consistent associations with corticosteroid responsiveness, though effect sizes are modest and lack large randomized validation. ADRB2 and leukotriene pathway variants demonstrate limited and inconsistent clinical value, while pharmacogenomic predictors of biologic therapy remain preliminary. An integrated clinical implementation pathway is proposed, emphasizing the need to interpret genetic results alongside inflammatory endotypes, adherence patterns, environmental exposures, and real-world treatment behaviour. Equity and ancestry considerations highlight the limited external validity of current findings, especially in underrepresented populations such as those in South Asia. Digital health technologies, pragmatic trials, and multi-omics integration represent promising directions for future research. Overall, while pharmacogenomics enhances mechanistic understanding of asthma, its present clinical utility is limited; meaningful translation will require expanded population diversity, stronger real-world evidence, and multi-dimensional predictive models that integrate genetics with biomarkers and digital health data.