Improvements in context-specific programming are essential to address HIV and other sexually transmitted and blood-borne infection epidemics globally. A programme science approach emphasises the need for context-specific evidence and knowledge, generated on an ongoing basis, to inform timely and appropriate programmatic decisions. We aim to accelerate and improve the use of embedded research, inquiry, and learning to optimise population-level impact of public health programmes and to introduce an effective programme coverage framework as one tool to facilitate this goal. The framework was developed in partnership with public health experts in HIV and sexually transmitted and blood-borne infections through several workshops and meetings. The framework is a practice-based tool that centres on the use of data from iterative cycles of programme-embedded research and learning, as well as routine programme monitoring, to refine the strategy and implementation of a programme. This programme science approach aims to reduce programme coverage gaps, to optimise impact at the population level, and to achieve effective coverage. This framework should facilitate the generation of programme-embedded research and learning agendas to inform resource allocation, optimise population-level impact, and achieve equitable and effective programme coverage.