Introduction: Cleft lip and palate are common craniofacial deformities and arise from disruption of complex epithelial and mesenchymal interactions during early embryonic development. Normal midfacial formation depends on tightly regulated morphogenetic signalling pathways guiding growth and fusion of the frontonasal and maxillary processes. Disruption of these processes may result in orofacial clefting. Over 300 genes have been implicated in palatal fusion, with clefting caused by mutations across multiple molecular pathways. Although several syndromic forms are well characterised, the aetiology of cleft lip and palate remains heterogeneous and multifactorial. Methods: This longitudinal study investigates the molecular and genetic mechanisms underlying cleft lip and palate 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 collected alongside biospecimens. Results: Genomic sequencing identified pathogenic variants in genes previously associated with cleft lip and palate, consistent with existing literature. Ongoing recruitment and analysis are enabling further characterisation of phenotypic and genotypic variability. Preliminary findings demonstrate the feasibility of correlating molecular data with clinical presentation in both syndromic and non-syndromic cases. Conclusion: This biobanking project provides a valuable resource for the longitudinal study of cleft lip and palate. With continued sample accrual, the study aims to identify molecular or genetic indicators predictive of syndromic clefting, particularly in newborns, to support earlier diagnosis and improved clinical management.