Pharmacogenomics—the study of how genetic variation influences drug response—has emerged as a cornerstone of precision oncology, enabling clinicians to tailor cancer therapies based on individual genomic profiles. As cancer treatment costs escalate globally, the integration of pharmacogenomics into oncology care presents a dual opportunity: enhancing therapeutic efficacy while simultaneously reducing economic waste associated with trial-and-error prescribing, adverse drug reactions, and suboptimal outcomes. This research evaluates the economic viability of pharmacogenomics integration in oncology from a health systems perspective, with a particular focus on its impact on cost reduction and clinical value. Employing a cost-effectiveness analysis framework, the study reviews current evidence on the economic impact of pharmacogenomics-guided therapies across various cancers, including breast, lung, and colorectal cancers. It incorporates quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and healthcare utilization metrics to assess economic feasibility. Additionally, system-level barriers—such as reimbursement limitations, lack of standardized testing protocols, and disparities in genomic literacy among healthcare professionals—are examined. Findings suggest that upfront investment in pharmacogenomic testing can lead to long-term cost savings by preventing adverse drug events and improving progression-free survival rates. Moreover, the study identifies policy levers, such as value-based pricing models and public-private partnerships, that can facilitate broader adoption. Ultimately, the integration of pharmacogenomics in oncology represents not only a scientific advancement but also a strategic policy and economic decision. Policymakers and healthcare administrators must recognize its potential to optimize both fiscal sustainability and patient-centered outcomes in cancer care.