Preprint article submitted to a peer-reviewed journal. This version has not yet undergone peer review. Abstract Precision oncology knowledge bases are central to interpreting cancer genomic variants and associating them with clinical implications, guiding therapeutic selection and molecular tumor board deliberations. Although clinical evidence informing these resources are broadly globally applicable, drug approvals and patient access to therapies are governed by regional regulatory and health system authorities. Currently, publicly available knowledge bases primarily represent regulatory approvals from the United States (US) Food and Drug Administration (FDA). Consequently, they may recommend inaccessible therapies or omit regionally approved options, limiting clinical utility in non-US settings. This disparity highlights an urgent need for region-specific precision oncology knowledge bases that account for local regulation and access. Here, we outline essential steps for establishing region-specific precision oncology knowledge bases by curating cancer drug approvals that have received local market authorization or reimbursement within their local health system. We do so in a project-agnostic manner to encourage distributed deployment, while also recommending the adoption of representation standards to support global interoperability. We envision a federated ecosystem of regionally contextualized knowledge bases that enable comparative analyses, which may provide a means to identify regional differences in treatment eligibility and pharmacoeconomic determinants of access. Building such frameworks will advance equitable precision oncology and ensure that genomic-driven cancer care benefits patients globally.