Purpose <p>The aim of the study was to evaluate the value of ¹⁸F-FDG PET/CT metabolic parameters in neuroblastoma (NB) with MYCN gain.</p> Methods <p>A retrospective analysis was conducted on 87 patients with NB (29 with MYCN gain and 58 with MYCN normal). The region of interest of primary tumors were manually delineated using 3D slicer<i>™</i> software, and ¹⁸F-FDG PET/CT metabolic parameters, including SUV_max, SUV_peak, SUV_mean, MTV and TLG were extracted. Logistic regression analyses were used to identify the relationship between ¹⁸F-FDG PET/CT metabolic parameters and MYCN gain. Cox proportional hazards regression models were used to assess the associations between ¹⁸F-FDG PET/CT metabolic parameters and EFS and OS. Survival curves were generated using the Kaplan-Meier method, and differences in survival between groups were compared using the log-rank test.</p> Results <p>A total of 87 NB patients [median age: 40 (20–56) months; 48 girls and 39 boys] were evaluated. Logistic regression analyses revealed that MTV (&gt;133.3 cm³) was an independent predictor of MYCN gain. During the follow-up period of 22 (2–70) months, 21 patients died and 37 patients experienced disease recurrence or progression. Cox proportional hazards regression analyses showed that MTV, in combination with PHOX2B, was an independent prognostic factor for EFS and OS in NB patients with MYCN-gain. Patients with high MTV exhibited significantly shorter EFS and OS compared to those with low MTV.</p> Conclusion <p>The volumetric parameter MTV derived from ¹⁸F-FDG PET/CT imaging can predict MYCN gain in NB patients and provide valuable prognostic information for patients with MYCN-gain NB.</p> Graphical Abstract <p></p>