Purpose <p>Precision cancer medicine (PCM), targeting cancer treatment to patients’ individual genomic profiles, has the potential to improve diagnosis and outcomes substantially. Implementing PCM in healthcare systems requires that extended molecular diagnostics are accessible as part of routine practice. We conducted a mixed-methods study to identify and inform the infrastructure necessary for the implementation of extended molecular diagnostics as part of the health care system.</p> Methods <p>To identify and inform relevant categories of necessary infrastructure, we combined a survey, a structured literature search, and expert interviews. The survey included questions on reimbursement and technology assessment of diagnostics for PCM. Findings from the structured literature search were grouped to identify categories of infrastructure together with emerging themes in interviews with experienced oncologists, pathologists, and health technology assessment experts.</p> Results <p>44 respondents from 20 countries participated in our survey. We identified and included 45 published papers, and seven experts were interviewed. We identified six key categories for implementing PCM as part of the healthcare system: physical, financial, organisational, competency, data and legal infrastructure. Our combined data sources revealed several themes to promote implementation, including the importance of centralisation of testing, the need for sustainable reimbursement, engagement of relevant stakeholders, interoperability of data infrastructure, and inter-disciplinary collaboration.</p> Conclusion <p>Our results highlight the need for interdisciplinary approaches and the value of initiatives to establish infrastructure within and across countries. While several European countries have come a long way in implementing diagnostics for PCM, considerable work remains to ensure equitable access for patients in need.</p>