As the need for a more rapid and efficient means of rigorous clinical evidence generated about medical products from diverse practice settings increases, so has interest in point-of-care (POC) clinical trials. Yet, although interest in and technical capabilities to support POC trials continues to rise, actual implementation of scaled, impactful POC platforms remains limited. The Duke-Margolis Real-World Evidence (RWE) Collaborative Point-of-Care Trials Working Group outlines steps to enable point-of-care trials to achieve their potential. First, we propose a definitional framework for point-of-care clinical trials, discuss what constitutes a point-of-care clinical trial, and illustrate the applicability of our proposed approach. Then, we identify factors impacting point-of-care trial feasibility, along with possible solutions to the impediments presented by each factor. Overall, our paper provides a roadmap to improving the feasibility and scalability of point-of-care trials.