Regulatory focus theory (Higgins, 1997) has attracted increasing attention in management and organizational behavior research. Building on and expanding upon the current application of regulatory focus theory, we develop a theory-driven nomological network of regulatory focus to comprehensively understand its predictors and outcomes and to unravel the mechanisms and boundary conditions for its implications. Specifically, our meta-analysis aims to: (a) summarize demographic, dispositional, and contextual antecedents and various outcomes of regulatory focus, (b) investigate the processes (i.e., work engagement and emotional exhaustion) underlying regulatory focus effects, and (c) explore theoretical (i.e., cultural individualism-collectivism) and methodological moderators (i.e., regulatory focus types and behavioral rating sources) for regulatory focus implications. Based on 213 articles with 250 samples and 70,673 participants from 30 countries/regions, we found that individual dispositions and contextual factors of leadership and job characteristics were meaningful predictors of regulatory focus. Promotion focus influenced distal attitudinal and behavioral outcomes (except task performance) via both work engagement and emotional exhaustion, whereas prevention focus affected distal work outcomes via work engagement but not via emotional exhaustion. Additionally, the fit between prevention focus and national collectivist cultures enhanced work engagement and reduced emotional exhaustion. Common method bias inflated the relationships between promotion focus and work behaviors. Our findings have important theoretical and practical implications.