Cardiovascular disease and hypercholesterolemia present significant global health and economic burdens. While statins are the standard treatment, individual variability and toxicities necessitate personalized approaches. This narrative review (2013-2025) evaluated the economic landscape of pharmacogenomics (PGx)-guided statin therapy and factors influencing its cost-effectiveness. Out of 219 studies, only four relevant evaluations were identified, all focusing on North American (United States & Canada) cohorts and published before 2019. Most models relied on literature-based simulations and utility data, introducing significant parameter uncertainty. Nevertheless, PGx-guided strategies generally proved cost-effective or dominant, particularly at higher willingness-to-pay thresholds, such as $50,000/QALY. In conclusion, PGx-guided therapy offers a viable pathway for improving clinical outcomes and economic efficiency. However, a paucity of raw clinical data and geographic diversity currently limit its standardized adoption. Future research must leverage real-world evidence from ongoing trials to inform robust, value-based healthcare policy.