Purpose: This study aimed to evaluate the ability of F-18 -FDG PET/CT metabolic parameters to predict the histological response to neoadjuvant chemotherapy in patients with osteosarcoma and Ewing sarcoma. Patients and methods: This systematic review and network meta-analysis adhered to the PRISMA-NMA and Cochrane guidelines. Electronic databases were searched from January 2008 to January 2024; this search was supplemented by snowballing methods. The risk of bias was evaluated with QUADAS-2, and evidence certainty was assessed using the GRADE approach. The prognostic value of 18 F-FDG PET/CT parameters, including pretreatment and posttreatment SUVs (SUV1, SUV2 and the SUV2/SUV1 ratio), metabolic tumor volume (MTV1, MTV2, Delta MTV), and total lesion glycolysis (TLG1, TLG2, Delta TLG), was examined. Results: The meta-analysis of (18) studies (714 patients) identified the Delta TLG, Delta MTV, and SUV ratio as superior predictors of histological response. The changes in metabolic activity, as indicated by these parameters, provided a robust indication of treatment effectiveness. Baseline parameters showed limited predictive value compared with posttreatment assessments. The study's robustness was confirmed through meta-regression, which revealed that the predictive value of the SUV2 and SUV ratio was consistent across various cutoff thresholds. Conclusions: F-18 -FDG PET/CT metabolic parameters, particularly those measuring changes posttherapy, are effective in predicting the histological response in patients with osteosarcoma and Ewing sarcoma. These findings underscore the potential of (18) F-FDG PET/CT in guiding early treatment decisions, thereby enhancing personalized therapeutic approaches.