Extreme heat and hot weather has a negative impact on human health and society. Global warming has resulted in an increase in the frequency and duration of heatwaves. Heat-related illnesses are a significant negative consequence of high temperatures and can be life-threatening medical emergencies. The severity of the symptoms can depend on the pre-existing medical conditions and vary from mild headaches to severe cases that can lead to coma and death. The risk of heat-related illness may be higher for people experiencing homelessness due to a lack of access to cool places and water, and the complex interactions between mental illness, medications and substance use disorder. This paper presents two cases of people experiencing homelessness who were admitted to the emergency department of a hospital in Sydney, Australia during a heatwave in November 2020. Both cases were adult males with known risk factors for heat-related illness including hypertension and schizophrenia (Case One) and hepatitis C, cirrhosis, and alcohol use disorder (Case Two). These cases show that severe weather can not only be detrimental to homeless people’s health but can also cause a significant economic toll, evident by the $70,184 AUD expenditure on the care for these two cases. This case report highlights the requirement to determine the risk of heat-related illness to people experiencing homelessness and need to protect this vulnerable population from weather-related illness and death.