The practice of science entails more than just repeated cycles of theory construction, hypothesis generation, and empirical investigation. Broader, metatheoretical levels of conceptualization necessarily condition all aspects of the research process, establishing the very meaning and sensibility of science’s empirical and theoretical activities. When debate arises at these metatheoretical levels, it is the subject of conceptual analysis, not empirical investigation. In this article, we examine the overarching metatheoretical divide that lies at the heart of many key theoretical debates in science: the divide between a Cartesian-Split-Mechanistic research paradigm and a Process-Relational research paradigm. We instantiate this divide in terms of three prominent domains of inquiry within developmental science: the study of epigenesis (including epigenetics); the study of embodiment, specifically embodied cognition; and the study of baselines for human nature and development. We reveal how core issues and theoretical debates within these domains derive from metatheoretical, not theoretical, points of contention.