This article provides a guide for rigorous, theory-driven measurement approaches, proposing best practices for the scientific study of systemic racism in health research. We argue that the analytical crux of measuring systemic racism—a complex, interconnected, and dynamic system—lies in operationalizing the collective logics, properties, and mechanisms that undergird racial inequities. Misalignment between measurement tools and these foundational features undermines research validity, as incongruent measures distort findings and obscure systemic racism’s true impacts. To address this, we draw on interdisciplinary theories and evidence to dissect key features of systemic racism, emphasizing their implications for measurement. We further recommend incorporating temporal processes in health research by leveraging core principles of the life course perspective, which elucidate the intricate interplay of individual, historical, and societal trajectories. Our recommendations underscore the necessity of adopting robust, evidence-based methods to advance the understanding of how systemic racism operates and shapes public health.