Objective: Precision medicine allows healthcare interventions to be tailored to groups of patients based on their disease susceptibility, diagnostic or prognostic information, or treatment response. We analysed what developments are expected in precision medicine over the next decade and considered the implications for health technology assessment (HTA) agencies. Methods: We performed a pragmatic literature search to account for the large size and wide scope of the precision medicine literature. We refined and enriched these results with a series of expert interviews up to 1 h in length, including representatives from HTA agencies, research councils and researchers designed to cover a wide spectrum of precision medicine applications and research. Results: We identified 31 relevant papers and interviewed 13 experts. We found that three types of precision medicine are expected to emerge in clinical practice: complex algorithms, digital health applications and ‘omics’-based tests. These are expected to impact upon each stage of the HTA process, from scoping and modelling through to decision-making and review. The complex and uncertain treatment pathways associated with patient stratification and fast-paced technological innovation are central to these effects. Discussion: Innovation in precision medicine promises substantial benefits but will change the way in which some health services are delivered and evaluated. The shelf life of guidance may decrease, structural uncertainty may increase and new equity considerations will emerge. As biomarker discovery accelerates and artificial intelligence-based technologies emerge, refinements to the methods and processes of evidence assessments will help to adapt and maintain the objective of investing in healthcare that is value for money.