BackgroundMental illness costs the world economy over US2.5 Bn each year, including premature mortality, morbidity, and productivity losses. Multisector approaches are required to address the systemic drivers of mental health and ensure adequate service provision. There is an important role for economics to support priority setting, identify best value investments and inform optimal implementation. Mental health can be defined as a complex dynamic system where decision makers are challenged to prospectively manage the system over time. This protocol describes the approach to equip eight system dynamics (SD) models across Australia to support priority setting and guide portfolio investment decisions, tailored to local implementation context.MethodsAs part of a multidisciplinary team, three interlinked protocols are developed; (i) the participatory process to codesign the models with local stakeholders and identify interventions for implementation, (ii) the technical protocol to develop the SD models to simulate the dynamics of the local population, drivers of mental health, the service system and clinical outcomes, and (iii) the economic protocol to detail how the SD models will be equipped to undertake a suite of economic analysis, incorporating health and societal perspectives. Models will estimate the cost of mental illness, inclusive of service costs (health and other sectors, where necessary), quality-adjusted life years (QALYs) lost, productivity costs and carer costs. To assess the value of investing (disinvesting) in interventions, economic analysis will include return-on-investment, cost-utility, cost benefit, and budget impact to inform affordability. Economic metrics are expected to be dynamic, conditional upon changing population demographics, service system capacities and the mix of interventions when synergetic or antagonistic interactions. To support priority setting, a portfolio approach will identify best value combinations of interventions, relative to a defined budget(s). User friendly dashboards will guide decision makers to use the SD models to inform resource allocation and generate business cases for funding.DiscussionEquipping SD models to undertake economic analysis is intended to support local priority setting and help optimise implementation regarding the best value mix of investments, timing and scale. The objectives are to improve allocative efficiency, increase mental health and economic productivity.