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In recent years, the focus of implementation science (IS) shifted to emphasize the influence of contextual factors on intervention adaptations in clinical, community, and corporate settings. Each of these settings represent a unique work system with varying contexts that influence human capabilities, needs, and performance (otherwise known as “human factors”). The ease of human interaction with a work system or an intervention is imperative to IS outcomes, particularly adoption, implementation, and maintenance. Both scientific approaches consider the “big picture” when designing interventions for users and stakeholders to improve work and health outcomes. IS and human factors are therefore complementary in nature. In this paper, the authors will (1) provide perspective on the synergistic relationship between human factors and IS using two illustrative and applied cases and (2) outline practical considerations for human factors-based strategies to identify contextual factors that influence intervention adoption, implementation, and maintenance dimensions of the RE-AIM framework. This article expands on recent research that developed user- and human-centered design strategies for IS scientists to use. However, defining the complementary relationship between IS and human factors is a necessary and valuable step in maximizing the effectiveness of IS to transform healthcare. While IS can complement practitioners' identification of intervention adaptations, human interaction is a process in the work system often overlooked throughout implementation. Further work is needed to address the influence that organizational endorsement and trust …