Our study shows the technical feasibility of integrating functional precision medicine approaches for patients with refractory/relapsed pediatric cancers. Routine clinical integration of FPM for treatment selection is technically feasible and has led to improved outcomes in pediatric cancer patients with refractory disease in an initial patient cohort. We are enrolling advanced cancer patients for FPM feasibility studies from pediatric/adolescent populations through Nicklaus Children’s Hospital (NCT05857969, n = 65 patients) and adult populations through Cleveland Clinic Florida (NCT06024603, n = 36 patients). The inclusion of patient tissue samples procured via fine-needle or core biopsy techniques, in addition to surgical resections, enables access to FPM approaches for patients where surgical resection is not viable or considered part of the standard of care. We are currently undergoing CLIA validation for the drug sensitivity testing assay in the FPM program, with the goal of initiating large-scale randomized clinical trials and providing treatment options to patients nationally and globally.