Background: The aim of this systematic review and meta-analysis was to determine the fracture resistance and survival rate of partial indirect restorations inlays, onlays, and overlays fabricated using computer-aided design and computer-aided manufacturing (CAD-CAM) technology from ceramics, composite resin, resin nanoceramic, or hybrid ceramic and to analyze the influence of proximal box elevation on fracture resistance. Materials and methods: This systematic review was based on guidelines proposed by the preferred reporting items for systematic reviews and meta-analyses (PRISMA). An electronic search was conducted in databases US National Library of Medicine National Institutes of Health (PubMed), Scopus, Web of Science (WOS), and Embase. In vitro trials published during the last 10 years were included in the review. Results: Applying inclusion criteria based on the review’s population, intervention, comparison, outcome (PICO) question, 13 articles were selected. Meta-analysis by restoration type estimated the fracture resistance of inlays to be 1923.45 Newtons (N); of onlays 1644 N and of overlays 1383.6 N. Meta-analysis by restoration material obtained an estimated fracture resistance for ceramic of 1529.5 N, for composite resin of 1600 Ne, for resin nanoceramic 2478.7 N, and hybrid ceramic 2108 N. Conclusions: Resin nanoceramic inlays present significantly higher fracture resistance values. Proximal box elevation does not exert any influence on the fracture resistance of indirect restorations.