Purpose: Few studies have focused on the feasibility and accuracy of intraoral digital impressions for maxillectomy defects, especially for extensive soft tissue defects. Using intraoral scanners alone might be feasible for producing maxillary obturator prostheses, albeit with some limitations. It seems logical to investigate this ambiguity. Therefore, this systematic review aimed to assessing the feasibility and accuracy of using intraoral scanners (IOSs) to digitize maxillectomy defects. Materials and Methods: PubMed, the Cochrane Oral Health Group Trials Register, and the Cochrane Central Register of Controlled Trials were electronically searched, and five prosthodontics journals were manually searched for English-language articles published as of December 2020 that assessed the feasibility and accuracy of using intraoral scanners to acquire digital impressions for maxillectomy defects. Results: Two in vitro studies, three clinical studies, six clinical reports, and three techniques were included (N=14). Aramany’s and Brown’s classifications were used to classify defects in twelve and one articles, respectively; the remaining article did not specify defect class. The 3M True definition IOS with Cone-beam computed tomography (CBCT), Computed tomography (CT), and/or optical scanners were used in both in vitro studies, mainly to evaluate accuracy. The Trios 3 scanner was used in nine studies as the main resource for data acquisition (75.0%), whereas the Trophy 3DI, Lava, and Cerec Omnicam scanners were used in three articles (25.0%). Four degrees of feasibility were identified: feasible (14.3%), feasible with limitations (28.6%), feasible with CBCT or CT (35.7%), and feasible with conventional impressions (21.4%). Accuracy was evaluated in four studies but was not mentioned in ten studies. Conclusion: The results revealed a low level of evidence for the feasibility and accuracy of using intraoral scanners to digitize maxillectomy defects. Additional multicenter clinical studies are needed to evaluate the feasibility and accuracy of digital workflow compared with the conventional approach.