Approved treatments for patients with refractory and/or relapsed (R/R) high-risk (HR) neuroblastoma are limited, and there is a high unmet need for new treatment combinations. The Atrium Health Levine Children’s Hospital pediatric oncology solid tumor team has successfully treated ten patients with R/R HR neuroblastoma with the anti-disialoganglioside 2 antibody naxitamab with granulocyte-macrophage colony-stimulating factor (GM-CSF), and four patients with naxitamab and GM-CSF in combination with cyclophosphamide and topotecan. Antibody therapy with chemoimmunotherapy was well tolerated in the four heavily pre-treated patients with R/R HR neuroblastoma who had few treatment options and overall poor prognosis.