Purpose: The purpose of this systematic review and meta-analysis was to compare the influence of fabrication method (conventional, subtractive, and additive procedures) and manufacturing trinomial (technology, printer, and material combination) on the marginal and internal fit of cobaltchromium (Co-Cr) tooth-supported frameworks. Materials and Methods: An electronic systematic review was performed in five data bases: MEDLINE/PubMed, Embase, World of Science, Cochrane, and Scopus. Studies that reported the marginal and internal discrepancies of tooth-supported Co-Cr additive manufacturing (AM) frameworks were included. Two authors independently completed the quality assessment of the studies by applying the Joanna Briggs Institute Critical appraisal Checklist for Quasi-Experimental Studies. A third examiner was consulted to resolve lack of consensus. Results: A total of 31 articles were included and classified based on the evaluation method: manufacturing accuracy, the dual- or triple-scan method, stereomicroscope, optical coordinate measurement machine, microCT, profilometer, and silicone replica. Six subgroups were created: 3D Systems, Bego, Concept Laser, EOS, Kulzer, and Sisma. Due to the heterogeneity and limited data available, only the silicone replica group was considered for meta-analysis. The meta-analysis showed a mean marginal discrepancy of 91.09 μm (I2 = 95%, P < .001) in the conventional group, 77.48 μm (I2 = 99%, P < .001) in the milling group, and 82.92 μm (I2 = 98%, P < .001) in the printing group. Additionally, a mean internal discrepancy of 111.29 μm (I2 = 94%, P < .001) was obtained in the conventional casting group, 121.96 μm (I2 = 100%, P < .001) in the milling group, and 121.25 μm (I2 = 99%, P < .001) in the printing group. Conclusions: Manufacturing method and selective laser melting (SLM) metal manufacturing trinomial did not impact the marginal and internal discrepancies of Co-Cr frameworks for the fabrication of tooth-supported restorations.