Background: Anemia is a common complication in children on hemodialysis, and erythropoietin resistance contributes to its management challenges. Objective: This study aimed to evaluate the role of residual kidney function (RKF) in predicting erythropoietin responsiveness in pediatric patients on regular hemodialysis. Methods: This cross-sectional cohort study included 40 children with a mean age of 15 ± 5 years on regular hemodialysis at Sohag University Hospital. The study was conducted from April 2022 to March 2023. Patients were classified as having preserved RKF (urine output >100 mL/m²/day) or no RKF. Erythropoietin resistance index (ERI), hemoglobin levels, and other clinical and laboratory parameters were compared between the two groups. Results: Of the 40 patients, 23 (57.5%) had preserved RKF, while 17 (42.5%) did not. Patients with RKF showed significantly higher hemoglobin levels compared to those without RKF (11.71 ± 2.62 g/dL vs. 8.82 ± 1.42 g/dL, p = 0.002 respectively) and lower ERI (0.97 ± 0.67 vs. 1.89 ± 1.12 IU/kg/g/dl, p < 0.002 respectively). The average erythropoietin dose was significantly lower in patients with RKF (268.3 ± 101.5 IU/kg/week) than in those without RKF (388.5 ± 67.3 IU/kg/week, p < 0.001). Growth parameters were better in patients with RKF, with a significant difference in height percentiles (p = 0.04). No significant differences were observed in iron profile and metabolic bone parameters, or dialysis adequacy between the two groups. Conclusions: Preservation of RKF in pediatric hemodialysis patients is associated with better anemia management, lower erythropoietin requirements, and improved growth outcomes. Strategies to preserve RKF should be emphasized to enhance patient prognosis and quality of life.