Global guidelines for new technologies are based on cost and efficacy data from a limited number of trial locations. Country‐level decision makers need to consider whether cost‐effectiveness analysis used to inform global guidelines are sufficient for their situation or whether to use models that adjust cost‐effectiveness results taking into account setting‐specific epidemiological and cost heterogeneity. However, demand and supply constraints will also impact cost‐effectiveness by influencing the standard of care and the use and implementation of any new technology. These constraints may also vary substantially by setting. We present two case studies of economic evaluations of the introduction of new diagnostics for malaria and tuberculosis control. These case studies are used to analyse how the scope of economic evaluations of each technology expanded to account for and then address demand and supply constraints over time. We use these case studies to inform a conceptual framework that can be used to explore the characteristics of intervention complexity and the influence of demand and supply constraints. Finally, we describe a number of feasible steps that researchers who wish to apply our framework in cost‐effectiveness analyses.