Advances in research on current and projected heat-related risks from climate change and the associated responses have rapidly developed over the past decade. Modelling architectures of climate impacts and heat-related health risks have become increasingly sophisticated alongside a growing number of experiments and socioeconomic studies, and possible options for heat-related health adaptation are increasingly being catalogued and assessed. However, despite this progress, these efforts often remain isolated streams of research, substantially hampering our ability to contribute to evidence-informed decision making on responding to heat-related health risks. We argue that the integration of scientific efforts towards more holistic research is urgently needed to tackle fragmented evidence and identify crucial knowledge gaps, so that health research can better anticipate and respond to heat-related health risks in the context of a changing climate. In this Personal View, we outline six building blocks, each constituting a research stream, but each needed as part of a more integrated research framework—namely, projected heat-related health risks; adaptation options; the feasibility and effectiveness of adaptation; synergies, trade-offs, and co-benefits of adaptation; adaptation limits and residual risks; and adaptation pathways. We outline their respective importance and discuss their benefits for health-related research and policy.