Low-income and middle-income countries account for over 80% of the world's infectious disease burden, but <20% of global expenditures on health. In this context, judicious resource allocation can mean the difference between life and death, not just for individual patients, but entire patient populations. Understanding the cost of healthcare delivery is a prerequisite for allocating health resources, such as staff and medicines, in a way that is effective, efficient, just and fair. Nevertheless, health costs are often poorly understood, undermining effectiveness and efficiency of service delivery. We outline shortcomings, and consequences, of common approaches to estimating the cost of healthcare in low-resource settings, as well as advantages of a newly introduced approach in healthcare known as time-driven activity-based costing (TDABC). TDABC is a patient-centred approach to cost analysis, meaning that it begins by studying the flow of individual patients through the health system, and measuring the human, equipment and facility resources used to treat the patients. The benefits of this approach are numerous: fewer assumptions need to be made, heterogeneity in expenditures can be studied, service delivery can be modelled and streamlined and stronger linkages can be established between resource allocation and health outcomes. TDABC has demonstrated significant benefits for improving health service delivery in high-income countries but has yet to be adopted in resource-limited settings. We provide an illustrative case study of its application throughout a network of hospitals in Haiti, as well as a simplified framework for policymakers to apply this approach in low-resource settings around the world.