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Abstract Background There is a fundamental gap in understanding the causal mechanisms by which strategies for implementing evidence-based practices address local barriers to effective, appropriate service delivery. Until this gap is addressed, scientific knowledge and practical guidance about which implementation strategies to use in which contexts will remain elusive. This research project aims to identify plausible strategy-mechanism linkages, develop causal models for mechanism evaluation, produce measures needed to evaluate such linkages, and make these models, methods, and measures available in a user-friendly website. The specific aims are as follows: (1) build a database of strategy-mechanism linkages and associated causal pathway diagrams, (2) develop psychometrically strong, pragmatic measures of mechanisms, and (3) develop and disseminate a website of implementation mechanisms knowledge for use by diverse stakeholders. Methods For the first aim, a combination of qualitative inquiry, expert panel methods, and causal pathway diagramming will be used to identify and confirm plausible strategy-mechanism linkages and articulate moderators, preconditions, and proximal and distal outcomes associated with those linkages. For the second aim, rapid-cycle measure development and testing methods will be employed to create reliable, valid, pragmatic measures of six mechanisms of common strategies for which no high-quality measures exist. For the third aim, we will develop a user-friendly website and searchable database that incorporates user-centered design, disseminating the final product using social marketing principles. Discussion Once strategy-mechanism linkages are identified using this multi-method approach, implementation scientists can use the searchable database to develop tailored implementation strategies and generate more robust evidence about which strategies work best in which contexts. Moreover, practitioners will be better able to select implementation strategies to address their specific implementation problems. New horizons in implementation strategy development, optimization, evaluation, and deployment are expected to be more attainable as a result of this research, which will lead to enhanced implementation of evidence-based interventions for cancer control, and ultimately improvements in patient outcomes.