A systematic review and meta-analysis was performed to analyze the survival of onlay restorations in the posterior region, their clinical behavior according to the material used (ceramic reinforced with lithium disilicate, conventional feldspathic ceramic or reinforced with leucite; hybrid materials and composite), possible complications, and the factors influencing restoration success. The systematic review was based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, without publication date or language restrictions. An electronic search was made in the PubMed, Scopus, Embase, and Cochrane databases. After discarding duplicate publications and studies that failed to meet the inclusion criteria, the articles were selected based on the population, intervention, comparison, outcome (PICO) question. The following variables were considered in the qualitative and quantitative analyses: restoration survival rate (determined by several clinical parameters), the influence of the material used upon the clinical behavior of the restorations, and the complications recorded over follow-up. A total of 29 articles were selected for the qualitative analysis and 27 for the quantitative analysis. The estimated restoration survival rate was 94.2%. The predictors of survival were the duration of follow-up (beta = −0.001; p = 0.001) and the onlay material used (beta = −0.064; p = 0.028). Composite onlays were associated with a lower survival rate over time. Onlays are a good, conservative, and predictable option for restoring dental defects in the posterior region, with a survival rate of over 90%. The survival rate decreases over time and with the use of composite as onlay material.