Introduction: Craniosynostosis is caused by the premature fusion of one or more cranial sutures, resulting in abnormal skull development and potential neurodevelopmental impairment. While it may occur as an isolated condition, craniosynostosis is frequently associated with genetic syndromes, with over 200 syndromes described to date. Advances in genomic analysis have improved understanding of its molecular basis, though significant phenotypic and genetic heterogeneity remains. Methods: This longitudinal study investigates the molecular and genetic pathways underlying craniosynostosis through the establishment of a paediatric biobank. Biological samples including blood, urine, and discarded surgical tissue were collected from patients undergoing surgical management. DNA and RNA extraction followed by PCR-based and genomic analyses were performed. Relevant clinical data were recorded alongside biospecimen collection. Results: Genomic sequencing identified pathogenic variants in genes previously associated with craniosynostosis, consistent with existing literature. Ongoing data collection is enabling further stratification of phenotypic and genotypic variability. Early findings support the feasibility of correlating molecular data with clinical presentation in both syndromic and non-syndromic cases. Conclusion: This biobank project provides a valuable resource for the longitudinal study of craniosynostosis. With continued sample accrual, the project aims to identify molecular or genetic indicators predictive of syndromic craniosynostosis, particularly in newborns, thereby supporting earlier diagnosis and improved clinical management.