Background <p>Frailty is a significant clinical syndrome affecting aging populations, leading to increased risks of negative outcomes such as falls, disability, hospitalization, and premature mortality. The concept has evolved from a simplistic view to a complex view that incorporates physical, psychological, cognitive, and social domains. Early intervention is crucial, yet research on the interactions among these domains is limited. This study protocol aims to outline various combinations of biological, psychosocial and nutritional interventions in prefrail older adults to address their effects on frailty status, including physical, psychological, and social functioning, nutritional status, and lifestyle changes over a 9-month intervention and follow-up period.</p> Methods <p>This study is a cluster-randomized controlled trial involving <i>N</i> = 308 prefrail older adults aged 60–80 from 32 community elderly centres in Hong Kong. Participants will be randomly selected and classified into four frailty deficit patterns. They will be assigned to one of four intervention strategies: biological/psychosocial/nutritional, biological/nutritional, psychosocial/nutritional, and inactive control. The intervention will focus on improving physical, psychological, and social functioning, nutritional status, and lifestyle changes over the 9-month period.</p> Discussion <p>This study is expected to provide substantial evidence on the effectiveness of these strategies in enhancing frailty status across bio-psycho-social domains in diverse elderly groups. The findings will have practical implications for healthcare professionals, caregivers, and policymakers, potentially leading to improved care and support for community-dwelling older adults in Hong Kong.</p> Trial registration <p>The trial has been registered in ClinicalTrials.gov under U.S. NIH (ID: NCT06741878, date: December 19, 2024).</p>