Congenital Zika Syndrome (CZS) is caused by vertical transmission of the Zika virus (ZIKV) during pregnancy, leading to various pathologies in affected fetuses. Although global ZIKV outbreaks have diminished, CZS remains a significant concern in endemic countries. Nowadays, CZS progression studies remain unexplored. To address this gap, we conducted a comprehensive study using in-vivo mice models to investigate the molecular mechanisms underlying CZS development, including acute and chronic infection stages. Our approach focused on examining proteome, N-glycoproteome, and phosphoproteome alterations across different neurodevelopmental stages. Through quantitative proteomics, N-glycoproteomics, and phosphoproteomics analyses, we detected 4,870 and 5,062 proteins in acute and chronic stages, respectively. Among them, 802 and 934 N-glycoproteins, 1,131 and 1,030 phosphoproteins, 1,786 and 2,188 N-glycosites, and 2,593 and 2,245 phosphosites, corresponding to acute and chronic infections. During early ZIKV infection, N-glycan biosynthesis was negatively disrupted through alpha-1,3/1,6-mannosyltransferase inhibition. The impairment of N-glycosylation may be related to proteasome activation in the acute stage. In the CZS stage, cell adhesion proteins exhibited a drastic hypoglycosylation affecting complex neurodevelopmental processes such as axonogenesis and synaptogenesis, also detected in the total proteomics approach. In addition, histological examination of postnatal ZIKV infection shows a decreased dendritic arborization of pyramidal neurons which may impact synapse formation. During acute stage, Golgi organization process was enhanced and regulated by phosphorylation, which might be related to N-glycosylation disruption. Conversely, the synaptic vesicle cycle was negatively modulated by phosphorylation in CZS stage. Among the dysregulated kinases, the phosphatidylinositol 4-kinase type 2-alpha, nucleoside diphosphate kinase B, cyclin-dependent kinase 2, and dual specificity protein kinase CLK2 remain altered throughout CZS development. Multi-proteomics approach proved to be a valuable tool to monitor CZS progression and allowed to identify specific proteins and pathways for potential therapeutic targeting.