The economic evaluation of health system interventions is challenging, and methods guidance on how to respond to these challenges is lacking. The REACHOUT consortium developed and evaluated complex interventions for community health program quality improvement in six countries in Africa and Asia. Reflecting on the challenges we faced in conducting an economic evaluation alongside REACHOUT, we developed a Structured Economic Evaluation Process for Complex Health System Interventions (SEEP-CI). The SEEP-CI aims to establish the threshold effect size that would justify investment in a complex intervention, and provide an assessment to a decision-maker of how likely it is that the intervention can achieve this impact. We illustrate how the SEEP-CI could have been applied to REACHOUT to identify outcomes where the intervention might have impact and causal mechanisms, through which that impact might occur, guide data collection by focusing on proximal outcomes most likely to illustrate the effectiveness of the intervention, identify the size of health gain required to justify investment in the intervention, and indicate the assumptions required to accept that such health gains are credible. Further research is required to determine the feasibility and acceptability of the SEEP-CI, and the contexts in which it could be used.