Clinical trials for oncology drug development have long relied on surrogate outcome biomarkers that assess changes in tumor burden to accelerate drug registration (i.e., Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria). Drug-induced reduction in tumor size represents an imperfect surrogate marker for drug activity and yet a radiologically determined objective response rate is a widely used endpoint for Phase 2 trials. With the addition of therapies targeting complex biological systems such as immune system and DNA damage repair pathways, incorporation of integrative response and outcome biomarkers may add more predictive value. We performed a review of the relevant literature in four representative tumor types (breast cancer, rectal cancer, lung cancer and glioblastoma) to assess the preparedness of volumetric and radiomics metrics as clinical trial endpoints. We identified three key areas-segmentation, validation and data sharing strategies-where concerted efforts are required to enable progress of volumetric- and radiomics-based clinical trial endpoints for wider clinical implementation.