OBJECTIVES: A better understanding of a patient’s genetic make-up through pharmacogenomic testing can help achieve improved and more predictable patient outcomes, often at equal or lower total treatment cost.  Stakeholders including physicians, payers and patients alike can benefit from real-world data that identify, a priori, the sub-groups of patients for whom treatments are likely to be more cost-effective. METHODS: Retrospective and prospective case study designs within which pharmacogenomic testing has been integrated are presented. Design parameters are described and opportunities and challenges alongside strategies for resolution are delineated. RESULTS: As the genetic make-up of a patient does not change, pharmacogenomic testing can be done at any point in time and paired with historical and/or newly collected patient level data. Retrospective studies are highly efficient as they do not require costly longitudinal follow-up, whereas prospective studies including registries offer the opportunity to augment pharmacogenomic and other study data with patient and physician reported outcomes not otherwise available in the medical chart. Main challenges associated with either approach include optimizing the patient informed consent process, streamlining the logistics associated with pharmacogenomic testing and storage in the usual care environment, and data analytics. CONCLUSIONS: The integration of pharmacogenomic testing with real-world studies offers an important opportunity to identify sub-groups of patients for whom treatment is more effective in terms of clinical, and safety outcomes. Alongside resource utilization and cost of care data, this evidence can be used to populate cost-effectiveness and other health economic analyses to inform physician and payer decision-making.