Purpose of Review Cost-effectiveness analysis (CEA) can help identify the trade-offs decision makers face when confronted with alternative courses of action for the implementation of public health strategies. Application of CEA alongside implementation scientific studies remains limited. We aimed to identify areas for future development in order to enhance the uptake and impact of model-based CEA in implementation scientific research. Recent Findings Important questions remain about how to broadly implement evidence-based public health interventions in routine practice. Establishing population-level implementation strategy components and distinct implementation phases, including planning for implementation, the time required to scale-up programs, and sustainment efforts required to maintain them, can help determine the data needed to quantify each of these elements. Model-based CEA can use these data to determine the added value associated with each of these elements across systems, settings, population subgroups, and levels of implementation to provide tailored guidance for evidence-based public health action. There is a need to integrate implementation science explicitly into CEA to adequately capture diverse real-world delivery contexts and make detailed, informed recommendations on the aspects of the implementation process that provide good value. Summary We describe examples of how model-based CEA can integrate implementation scientific concepts and evidence to help tailor evaluations to local context. We also propose six distinct domains for methodological advancement in order to enhance the uptake and impact of model-based cost-effectiveness analysis in implementation scientific research.