Background/Objectives: Maxillary defects, whether congenital or acquired, can compromise chewing, speech, and aesthetics. This systematic review aimed to evaluate the application and characteristics of definitive palatal obturators in the rehabilitation of such defects, analyzing techniques of fabrication, materials, outcomes of the fabrication, and limitations reported in the literature. Methods: The review was conducted in accordance with PRISMA 2020 guidelines and was registered in PROSPERO (ID: 1011648). A comprehensive search was performed in PubMed, Scopus, Lilacs, and Google Scholar for studies published from 1 January 2014 to 1 January 2025. Inclusion criteria comprised adult patients treated with definitive palatal obturators and with reported follow-up. Exclusion criteria included studies on children, animals, or lacking patient data. Two reviewers independently screened studies and assessed eligibility. Bias was evaluated qualitatively across five domains. No meta-analysis was conducted; data were synthesized descriptively using charts and tables. The study was funded by the Italian Ministry of Health—Current Research IRCCS. Results: A total of 59 studies involving 83 patients (46 males, 37 females; mean age 54.6 ± 13.8 years) were included. Mucormycosis and squamous cell carcinoma were the primary causes of defects. Conventional impressions using alginate and silicone were most common, while digital techniques were reported in only 6.6% of cases. All definitive obturators were fabricated using acrylic resin, with some featuring hollow bulbs, velopharyngeal extensions, or magnetic retention. Multiple sources of bias were observed. Conclusions: Definitive palatal obturators provide effective functional and aesthetic rehabilitation for maxillary defects. However, evidence is limited by methodological weaknesses, lack of standardization, and underutilization of digital technologies. Future studies should focus on improving reporting quality, adopting innovative fabrication protocols, and generating higher-level clinical evidence to support best practices.