Here, we elucidated that MNA neuroblastoma favors one carbon metabolism and purine biosynthesis by the up-regulation of MYCN-targeted metabolic genes MTHFD2 and PAICS. Our results also indicated that dual knockdown of MTHFD2/PAICS significantly reduced cell proliferation, colony formation, and migration which might diminish the aggressiveness and tumor progression ability in MNA neuroblastoma. Here, MYCN is linked to neoplasm.