Approved treatments for patients with refractory and/or relapsed (R/R) high-risk (HR) neuroblastoma are limited, and there is a need for new treatment combinations. In this case series, 4 patients were treated with the anti-GD2 monoclonal antibody naxitamab and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with cyclophosphamide and topotecan between August 2021 and December 2022. This combined chemoimmunotherapy regimen was well tolerated in these heavily pretreated patients with R/R HR neuroblastoma who had few treatment options and overall poor prognoses.