Abstract: An effective bond between a denture lining material and the denture base resin is necessary for proper function. Regarding the new technologies for manufacturing denture bases, a systematic search of the literature on this topic is lacking. The purpose of this systematic review and meta-analysis was to evaluate the bond strength between denture lining material and computer-aided design and computer-aided manufacturing (CAD-CAM) denture base resin (milled and 3-dimensionally printed) versus conventional denture base resin. Electronic databases (PubMed/MEDLINE, Scopus, and Web of Science) were independently searched by 4 researchers for relevant studies published up to April 2023. The population, intervention, comparison, and outcome (PICO) question was: "Comparing conventional and CAD-CAM (milled and 3-dimensionally printed) denture base materials, which promote greater bond strength when associated with denture lining material?" A meta-analysis was performed based on mean ±standard deviation bond strength values between denture base resins and denture lining material with 95% confidence intervals. Five in vitro studies were included. For bond strength, no difference was noted between conventional and milled denture base resin (confidence interval: -0.99 [-2.17 to 0.20]; heterogeneity: t2=0.57; Chi2:4.57; I2=78%; P=.10), and conventional resin had better values compared with those of 3-dimensionally (3D) printed (confidence interval: 3.03 [2.40-3.66]; heterogeneity: t2=0.00; Chi2:0.56; I2=0%; P<.001) when relined with soft materials. The milled denture base resin was better than the conventional (confidence interval: -0.85 [-1.33 to -0.38]; heterogeneity: Chi2:28.87; I2=93%; P<.001), with no difference between 3D printed and conventional (confidence interval: 0.18 [-4.23 to 4.59]; heterogeneity: t2=16.51; Chi2:130.99; I2=98%; P=.94) for hard liners. The bond strength between resins for milled CAD-CAM denture bases and denture lining material was similar to that of conventional denture base resin, regardless of the consistency of the denture lining material. The bond strength to 3D printed CAD-CAM resin was lower than that of the milled version Ver menos