PURPOSE: Neuroblastoma is a challenging pediatric tumor with a need for improved treatment strategies. This study explores the role of disulfidptosis, a form of cell death induced by intracellular disulfide accumulation, in neuroblastoma and its implications for prognosis and immune infiltration. METHODS: We subgrouped neuroblastoma samples based on disulfidptosis-related gene expression and constructed a disulfidptosis potential index (DPI) to quantify disulfidptosis levels in neurobalstoma. The correlation between DPI, outcome, immune infiltration, and drug sensitivity were explored. RESULTS: Combing RNA-seq and single-cell dataset, we found that higher disulfidptosis potential index (DPI) is associated with poorer outcomes in neuroblastoma patients, indicating the detrimental impact of enhanced disulfide stress and cellular dysfunction. Furthermore, we found that higher DPI is correlated with reduced immune infiltration within the tumor microenvironment, highlighting an immunosuppressive milieu in high DPI neuroblastomas. The DPI-high neuroblastoma may benefit from the estrogen pathway related drug fulvestrant. CONCLUSION: Overall, this study highlights the significance of disulfidptosis as a potential therapeutic target and underscores the importance of integrating immune modulation strategies, offering new avenues for improved management of neuroblastoma.