This systematic review examines the effectiveness of digital impressions in infants with cleft lip and palate (CLP), focusing on accuracy, operator preferences, and parents’ perceptions. The PICO-formulated focused questions assessed the accuracy and operator preference of digital impressions compared to conventional impressions in infants with cleft lip and palate, while also exploring parents’ perceptions as patient-centred outcomes. Electronic and manual searches were conducted in five databases including PubMed, Scopus, Web of Science, Embase, and Cochrane Library; to acquire grey literature, Google Scholar was also consulted. Both experimental and observational studies that used digital impressions in the clinical care of infants with CLP were included. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the quality of the included studies. Out of 503 records, 12 studies met the inclusion criteria. The accuracy assessment included surface discrepancy and intra-arch measurements. Surface discrepancy studies showed variations in the premaxillary segments, while intra-arch measurements revealed no significant differences. Operators preferred digital impressions, citing reduced stress and streamlined workflows. Parents expressed a clear preference for digital over conventional impressions. The conclusions drawn were substantiated by weak evidence due to the limited number and the high risk of bias of the included studies. Challenges remain here, warranting continued research to enhance accuracy and assess parents’ preferences, ensuring optimal outcomes for infants with CLP.