THERMOMICS, an FP7-funded project, addressed several mechanisms that may explain the sequence of events leading to heat stroke and death. The project’s objective was to identify whether the regulated index of human thermoregulation is temperature- of heat-based. The THERMOMICS experiments aimed at applying thermal stimuli in different bodily systems while making precise time-based measurements of temperature at different body areas as well as total body heat storage. This procedure generated evidence suggesting that the observed responses in each system correspond more appropriately to alterations in heat content and only to a lesser extent in temperature. Thermoregulation-related mortality is a significant public health issue even in temperate to warm climates. The benefit from the THERMOMICS research is noteworthy because it has increased our understanding of the pathophysiological mechanisms related to thermal stress and it has related the progressive changes in the thermal strain to inflammatory responses, and effects on the circadian rhythm and the sensory system.