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In the coordinate measuring machine (CMM) measurement environment, uncertainty can arise from various sources. Previous literature has focused on how to measure uncertainty in a CMM system using segregated approaches. We developed a framework to verify bias and variance tendencies deriving from form errors. Two types of form tolerances, namely flatness and circularity, are addressed here. By studying the nature of the CMM measurement uncertainty impact, this paper targets three objectives: (1) developing a design of experiments (DOE)-based measurement performance approach to integrate critical measurement strategy factors; (2) optimizing identified controllable measurement factors; and (3) synthesizing the impact of CMM uncertainty issues. Consequently, the paper fully explores the influence and interplay of these contributing factors, resulting in robust and optimal guidelines for the CMM flatness and circularity measurement strategy. Extensions of the framework for other form tolerances are discussed.