<p>Hybrid imaging is fundamental in the staging and response assessment of patients affected by neuroblastoma (NB). [¹²³I]-metaiodobenzylguanidine (MIBG) scintigraphy±single-photon emission computed tomography/computed tomography (SPECT/CT) is considered the gold standard for the evaluation of NB, but it presents some limitations, such as the time-consuming procedure (2&#xa0;days), the low spatial resolution, and challenging interpretation. Alternative positron emission tomography/computed tomography (PET/CT) catecholaminergic radiopharmaceuticals have been investigated to overtake the issues of [¹²³I]-MIBG. Among them, one of the most promising seems to be meta-[¹⁸F]fluorobenzylguanidine ([¹⁸F]-mFBG). Thus, we planned a head-to-head systematic review and meta-analysis to compare [¹⁸F]-mFBG PET/CT and [¹²³I]-MIBG SPECT/CT in NB. We executed a literature search to identify all articles performing a head-to-head comparison between these two methods, excluding review articles, preclinical studies, case reports, and small case series (less than 5 patients). Finally, five studies were collected for a total of 115 patients and 1,644 lesions. A patients-based analysis showed that [¹⁸F]-mFBG PET/CT had a higher pooled sensitivity than [¹²³I]-MIBG SPECT/CT (97% vs 82%, respectively) and identical pooled specificity (82%). Also at a lesion-based analysis, [¹⁸F]-mFBG PET/CT demonstrated better sensitivity (99% vs 51.5%). In conclusion, preliminary evidence-based data demonstrate that [¹⁸F]-mFBG PET/CT showed superior diagnostic performance than [¹²³I]-MIBG SPECT/CT. However, it is still unclear the real added value of [¹⁸F]-mFBG PET/CT compared to [¹²³I]-MIBG SPECT/CT in the change of clinical management. These findings suggest [¹⁸F]-mFBG PET/CT may become a superior, more efficient alternative to [¹²³I]-MIBG for staging and response assessment in neuroblastoma. Future studies should focus on its impact on clinical management and patient outcomes.</p> Graphical Abstract <p></p>