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Dynamic ultrasound indices assess preload-dependent changes in stroke volume via the Frank-Starling mechanism and guide fluid therapy. This study aimed to determine optimal cutoff values for ultrasound-derived peak aortic (ΔVAo) and carotid (ΔVCa) velocity variations to predict fluid responsiveness in critically ill pediatric oncology patients. In this prospective cohort, 83 children underwent 88 fluid challenges with 10 mL/kg saline. Fluid responsiveness was defined as a >15% increase in cardiac index, measured by left ventricular outflow tract Doppler after volume expansion. Fluid responsiveness occurred in 54.5% of assessments. ΔVAo demonstrated the highest predictive accuracy, with a 16.3% cutoff (sensitivity 91.6%, specificity 80%, AUC 0.89). ΔVCa showed moderate performance (cutoff 14.2%; sensitivity 79.1%, specificity 65%, AUC 0.75), while ΔIVC was not predictive (AUC 0.56). In mechanically ventilated patients (n = 60), ΔVAo remained accurate (cutoff 16.3%; AUC 0.90), whereas ΔVCa was modest (cutoff 16.5%; AUC 0.74). In spontaneously breathing patients (n = 28), ΔVAo cutoff was 15.5% (sensitivity 95%, specificity 87.5%, AUC 0.89), and ΔVCa was 13.2% (sensitivity 100%, specificity 50%, AUC 0.69). ΔVAo is a reliable predictor of fluid responsiveness in critically ill pediatric oncology patients. ΔVCa may serve as an alternative, though with lower accuracy.