Objectives Hematological toxicities are a common sequela of radiation therapy (RT), and pelvic RT is of particular concern as the pelvic marrow contributes nearly 50% of total body hematopoiesis. This study aims to evaluate the impact of pelvic RT on hematological toxicities in pediatric patients with pelvic genitourinary rhabdomyosarcoma (GU-RMS). Methods A secondary analysis was conducted on 488 pediatric patients with intermediate-risk rhabdomyosarcoma enrolled in the ARST0531 trial. Of these, 65 had pelvic GU-RMS and received pelvic RT. Multivariable logistic regression models were used to assess the odds of developing cytopenias (anemia, leukopenia, neutropenia, thrombocytopenia, and lymphopenia) during the study period (weeks 1-43). The analysis adjusted for variables such as age, race, tumor size, and chemotherapy regimen. Outcomes were compared between pelvic GU-RMS patients and non-GU RMS patients. Results GU-RMS patients did not have a significantly higher risk of developing cytopenias compared to non-GU RMS patients. Neutropenia was the most prevalent cytopenia, affecting 79.4% of subjects, with no significant difference between the GU (73.8%) and non-GU (80.4%) groups (OR 0.64,p=0.16). Thrombocytopenia was significantly more common in GU-RMS patients during the first 15 weeks (OR 2.79,p=0.01) of treatment. Febrile neutropenia and infectious complications were comparable between both groups across the study periods. Conclusion Comparable rates of hematological toxicities were observed in pediatric GU and non-GU RMS subjects. Pelvic RT for GU-RMS was associated with an early increase in thrombocytopenia risk, though this difference diminished over time. Further understanding these hematological toxicities is essential for improving the management of pediatric RMS patients.