<p>Pediatric oncology clinical trials (POCTs) are the cornerstone of therapeutic progress in childhood cancer. Yet, poor accrual and retention remain persistent challenges contributing to early termination of POCTs, limiting the advancement of novel therapies. These challenges reflect a convergence of system, protocol, clinician, and family-level factors, among which caregivers’ psychosocial decision-making processes represent a potentially modifiable but underexplored contributor. Caregivers making POCT-related decisions must navigate complex medical information under conditions of heightened emotional distress and uncertainty. Psychosocial factors such as distress, comprehension, trust, values, and social context are known to influence decision-making. However, the field still lacks an integrated framework to explain how these factors may shape decisional trajectories and outcomes throughout POCT participation. This commentary reframes POCT enrollment not as a discrete informed-consent event, but as a dynamic, psychosocial decision-making process that unfolds over time. We present an outline of a conceptual Precision Communication Framework designed to support care teams in aligning communication priorities with caregivers’ psychosocial and decisional contexts at key decision points throughout trial participation. Rather than seeking to address all causes of poor accrual or withdrawal, this framework focuses on reducing preventable decisional uncertainty and regret in contexts where psychosocial processes are central drivers of caregiver experiences. By presenting an outline of a conceptual model that would link psychosocial-decisional profiles to communication strategies to prioritize, this commentary aims to inform future empirical research and lay the groundwork for identifying communication strategies to prioritize to reduce caregiver decisional burden and promote sustained participation in POCTs.</p>