The influence of computer-aided manufacturing (CAM) parameters and settings on the outcomes of milled indirect restorations is poorly understood. The purpose of this scoping review was to summarize the current CAM systems, parameters, and setting changes, and their effects on different outcomes of milled indirect restorations and aspects related to their manufacture. The protocol of this review is available online (https://osf.io/x28ps/). Studies that used at least 2 different parameters (CAM units, number of axes, digital spacers, or protocols with different rotatory instruments, grit-sizes, milling speed, or others) for milling indirect restorations were included. A structured search up to July 2023 was performed by 2 independent reviewers for articles written in English in LILACS, MEDLINE via PubMed, EMBASE, Web of Science, and Scopus. Of 1546 studies identified, 22 were included in the review. Discrepancies were found between the planned and actual measured cement space, with a decreasing linear relationship impacting restoration adaptation at different points. The CEREC MC XL milling machine was the most used system in the included studies, with variations in bur types, milling modes, and number of burs uses affecting internal fit and surface trueness. The results demonstrated the better adaptation of restorations made with 5-axis over 3-axis milling machines. Lithium disilicate and zirconia were the most commonly used materials, and crowns and inlays were popular designs. Marginal and internal adaptation were the primary outcomes assessed using the various techniques. The study presented a comprehensive exploration of CAM systems and parameters, and their influence on indirect restorations. The planned cement space was not properly reproduced by the milling. Bur characteristics can affect restoration fit and trueness. The 5-axis units seem to result in better-adapted restorations compared with 3- and 4-axis units.