Objectives: Targeted therapy offers potential improvements in treatment costs and quality, yet its success hinges on the ability to accurately identify biomarker targets and ensure access to testing. This review aimed to understand global barriers to genomic testing utilization, in an effort to identify opportunities for intervention or education. Methods: A targeted literature review of PubMed, scientific conference proceedings, clinical guidelines, and payer coverage policies was conducted. Studies were identified from North America, European Union Five (EU5), Japan, and Australia. Sources that discussed the utilization of next-generation sequencing (NGS) and oncology biomarkers specific to breast cancer genes (BRCA), homologous recombination repair defects/mutation (HRRd/HRRm), or tumor mutation burden (TMB) were reviewed to identify barriers to optimal clinical use. Results: Despite the potential benefits of genomic testing, clinical utilization has been limited. The key barriers are inadequate reimbursement mechanisms, a lack of data supporting the tests’ clinical utility, limited adoption of genomic testing in patient care pathways and guidelines, and inadequate resources in clinical settings. Reimbursement concerns are related to the introduction of novel tests into established reimbursement structures. For example, using established coding to obtain reimbursement for genomic testing can be challenging and may necessitate the development of new codes, which can be a lengthy and cost-prohibitive process. Funding in some markets can be capped for specific therapeutic areas and bundled-payment or global payment structures may limit available funding for or investment in novel testing platforms. Further, an important determinant of initial payer coverage and physician adoption is proven clinical utility. However, the definition of “clinical utility” remains unclear across healthcare decision-makers. In turn, many clinical guidelines are slow to adopt genomic testing as part of recommended care. These concerns coupled with inadequate resources such as lacking standardized result reporting and limited physician genomic competency have made physicians less likely to use genomic testing. Conclusions: Despite the potential for genomic testing to improve patient diagnosis, management quality, and treatment costs, it remains greatly underutilized. Improving reimbursement mechanisms and clarifying clinical utility will be crucial for its optimal use.