Objectives: The hemodynamic profile of multisystem inflammatory syndrome in children (MIS-C)–related shock remains poorly defined and, therefore, challenging to support with pharmacotherapy in the ICU. We aimed to evaluate the hemodynamic profile and vasoactive medication management used in MIS-C patients presenting to the ICU in shock and provide data from high-fidelity continuous cardiac output monitoring. Design: Single-center retrospective case-cohort study. Setting: Pediatric and cardiac ICU in a quaternary-care hospital. Patients: All patients who met U.S. Centers for Disease Control and Prevention criteria for MIS-C and who were admitted to the ICU between March 2020 and May 2021 required vasoactive support and were placed on continuous cardiac index (CCI) monitoring. Patients requiring extracorporeal life support were excluded. Interventions: None. Measurements and Main Results: Among 52 children with MIS-C presenting in shock and requiring vasoactive support, 14 patients (27%) were placed on CCI monitoring. These 14 patients had hyperdynamic cardiac index (CI) and low indexed systemic vascular resistance (SVRi) in the first 24 hours with normalization of CI and improved SVRi within the subsequent 24 hours. Conclusions: Further studies are needed to evaluate the difference between the use of vasoconstrictor versus vasodilators in pediatric patients with MIS-C because a phenotype with high CI and low SVRi may be important.