BACKGROUND: Posterior fossa brain tumors (PFBT) are the most common solid tumor in children. Recent increases in survival rates are encouraging; however, survivors may experience a plethora of disease- and treatment-related complications that can persist into adulthood. Therapeutic exercise interventions have been shown to improve quality of survivorship in other pediatric cancer diagnoses. There is also evidence that goal-directed interventions are effective at improving motor activities, function, and self-care in children with complex health conditions. Yet, there is currently no evidence on the efficacy of goal-directed therapeutic exercise in pediatric PFBT survivors. The Physical ACTivity in Survivorship (PACTS) study aims to investigate the effects of a novel goal-directed therapeutic exercise program on cardiorespiratory fitness and physical activity-related goal attainment in pediatric survivors of PFBT. METHOD: PFBT survivors, aged five to 17 years, who underwent surgery at least 12 months earlier and completed radiation therapy and/or chemotherapy at least 6 months prior will be recruited from the Queensland Children's Hospital (Brisbane, Australia) (target n = 48). Following baseline assessment, participants are randomized into either the intervention or usual care group. The intervention group will receive weekly individualized, goal-directed exercise therapy delivered face-to-face for 12 weeks, along with an accompanying home-based program (three sessions per week). Outcomes will be assessed at baseline, immediately post-intervention, and at 6- and 12-months post-intervention. The primary outcomes are cardiorespiratory fitness (Peak VO2) and physical activity-related goal attainment. Secondary outcomes are cardiorespiratory endurance, high-level mobility skills, functional muscle strength, habitual physical activity, gait, balance, quality of life, fatigue, participation, perceived movement skill competence and parameters of body composition. DISCUSSION: PACTS is the first study to investigate the efficacy of goal-directed therapeutic exercise in children with PFBT and provide evidence needed to inform clinical practice recommendations for managing quality of survivorship in PFBT survivors. TRIAL REGISTRATION: ACTRN12619000841178 .