This systematic review and meta-analysis investigated the clinical outcomes of tooth-borne partial and full-coverage fixed dental restorations produced from hybrid polymer–ceramic CAD/CAM materials, with emphasis on biological, mechanical, and esthetic performance. Literature searches were conducted in MEDLINE using a PICOS framework, and randomized controlled trials as well as case-control studies were screened independently by two reviewers with MeSH terms. Study quality and risk of bias were assessed through the Cochrane Collaboration tool and the Newcastle–Ottawa Scale. Pooled analyses were carried out to compare long-term survival at two intervals (≤24 months and ≥36 months), and complication rates were examined with R software (p < 0.05). Twenty-eight studies were included in the qualitative synthesis, and 25 in the quantitative analysis. Pooled survival was 99% (0.95–1.00) at ≤24 months, declining to 95% (0.87–0.98) at ≥36 months. Success rates followed a similar trend, with 88% (0.54–0.98) at ≤24 months and 77% (0.62–0.88) at ≥36 months. Differences across follow-up periods and among biological, technical, and esthetic outcomes (88% vs. 77%; 90% vs. 74%; 96% vs. 95%) were not statistically significant. A significant effect, however, was detected in the technical performance, favoring full crowns (93%; 0.88–0.96) over partial crowns (64%; 0.34–0.86). Although not statistically significant, partial crowns also showed lower biological (69%; 0.42–0.87 vs. 91%; 0.79–0.97) and esthetic (90%; 0.65–0.98 vs. 99%; 0.92–1.00) success compared with full crowns.
