Objective: The aim of the study was to systematically review the overall outcomes of studies comparing the misfit of yttria-stabilized zirconia (Y-TZP) CAD-CAM implant-supported frameworks with frameworks fabricated with other materials and techniques. Methods: An electronic literature search of English literature was performed using Google Scholar, Scopus, Web of Science, MEDLINE (OVID), EMBASE, and PubMed, using predetermined inclusion criteria. Specific terms were utilized in conducting a search from the inception of the respective database up to May 2022. After the search strategy was applied, the data were extracted and the results were analyzed. The focused question was: Is the misfit of the implant-supported zirconia CAD-CAM framework lower than that of non-Y-TZP implant-supported fixed restorations? Results: Eleven articles were included for qualitative assessment and critical appraisal in this review. In the included studies, Y-TZP CAD-CAM implant-supported frameworks were compared to Titanium (Ti), Ni-Cr, Co-Cr, PEEK and high-density polymer, and cast and CAD-CAM frameworks. The studies used scanning electron microscopy, one-screw tests, digital or optical microscopy, 3D virtual assessment, and replica techniques for analyzing the misfit of frameworks. Six studies showed comparable misfits among the Y-TZP CAD-CAM frameworks and the controls. Three studies showed higher misfits for the Y-TZP CAD-CAM frameworks, whereas two studies reported lower misfits for Y-TZP CAD-CAM implant frameworks compared to controls. Conclusion: Y-TZP CAD-CAM implant-supported frameworks have comparable misfits to other implant-supported frameworks. However, due to heterogeneity in the methodologies of the included studies, the overall numerical misfit of the frameworks assessed in the reviewed studies is debatable View Full-Text ►▼ Show Figures This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.