Pharmacometrics is a powerful tool for analyzing sparse data to support precision pharmacotherapy. This approach is valuable for determining initial doses, analyzing blood levels collected during monitoring, and adjusting future dosing. Precision pharmacotherapy is crucial in both routine patient care and clinical trials. This dissertation presents two research projects that demonstrate how pharmacometrics can predict: 1) optimal antithrombin therapy in critically ill pediatric patients, and 2) the optimal timing for donor cell infusion during clinical testing for a new conditioning treatment. Extracorporeal membrane oxygenation (ECMO) support for critically ill pediatric patients is associated with an increased risk of thromboembolic events, and unfractionated heparin is commonly used for anticoagulation. Due to reports of acquired antithrombin (AT) deficiency in this patient population and concerns about heparin resistance, measuring AT activity and using off-label AT replacement have become common practices in pediatric ECMO centers, despite limited optimal dosing regimens. To characterize the PK of human plasma-derived AT under ECMO conditions, a retrospective cohort study was conducted on pediatric ECMO patients. The analysis demonstrated that ECMO can double the clearance and volume of AT. To prevent AT activity from falling below predetermined thresholds of 50% activity in neonates and 80% activity in infants and older children, optimal replacement regimens for each age group are proposed, accompanied by therapeutic drug monitoring. For successful engraftment of donor hematopoietic stem cells, conditioning with chemotherapy and/or radiation prior to hematopoietic cell transplantation (HCT) is required to clear the bone marrow and minimize the risk of immune rejection. Briquilimab, a humanized monoclonal antibody that blocks the interaction between the c-Kit receptor and stem cell factor on various c-Kit expressing tissues, including hematopoietic stem cells, is a potential nonmyeloablative conditioning agent in clinical development for patients with severe combined immunodeficiency, myelodysplastic syndromes, or acute myeloid leukemia. For successful donor cell engraftment, it is expected that the optimal timing for donor cell infusion is when briquilimab concentrations reach 500 – 2000 ng/mL following a single infusion of 0.6 mg/kg. PK analysis using data from three clinical studies demonstrated that a two-compartment model with linear and non-linear elimination pathways well characterized the briquilimab PK. Empirical Bayesian forecasting can guide the individualized timing for donor cell infusion based on sparse data.