Many public health challenges are characterized by complexity that reflects the dynamic systems in which they occur. Such systems involve multiple interdependent factors, actors, and sectors that influence health, and are a primary driver of challenges of insufficient implementation, sustainment, and scale of evidence-based public health interventions. Implementation science frameworks have been developed to help embed evidence-based interventions in diverse settings and identify key factors that facilitate or hinder implementation. These frameworks are largely static in that they do not explain the nature and dynamics of interrelationships among the identified determinants, nor how those determinants might change over time. Furthermore, most implementation science frameworks are top-down, deterministic, and linear, leaving critical gaps in understanding of both how to intervene on determinants of successful implementation and how to scale evidence-based solutions. Design thinking and systems science offer methods for transforming this problem-oriented paradigm into one that is solution-oriented. This article describes these two approaches and how they can be integrated into implementation science strategies to promote implementation, sustainment, and scaling of public health innovation, ultimately resulting in transformative systems changes that improve population health.