Despite the rise of decentralised trial models, clinical research delivery remains fundamentally dependent on sites. Yet the current U.S. site network is overburdened, under-resourced and increasingly strained by growing demand. To address unmet health needs and keep pace with advances in discovery science, the U.S. must expand and modernise its site ecosystem to increase capacity, accelerate patient recruitment and ensure patient representation better reflects real-world U.S. populations, in line with FDA FDORA requirements.