Heat illness results from the body’s impaired ability to regulate core temperature under thermal and exertional stress, leading to a cascade of physiological dysfunctions. This presentation will examine the underlying mechanisms of heat illness, with a focus on cardiovascular strain, thermoregulatory disruption, and systemic inflammation. Special emphasis will be placed on sex differences, highlighting recent insights into female-specific responses to heat stress and exertional heat stroke. These distinctions have critical implications for prevention and treatment strategies, particularly in athletic and military populations.