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Delivering heat in vivo could enhance a wide range of biomedical therapeutic and diagnostic technologies, including long-term drug delivery devices and cancer treatments. To date, providing thermal energy is highly power-intensive, rendering it oftentimes inaccessible outside of clinical settings. We developed an in vivo heating method based on the exothermic reaction between liquid-metal-activated aluminum and water. After establishing a method for consistent activation, we characterized the heat generation capabilities with thermal imaging and heat flux measurements. We then demonstrated one application of this reaction: to thermally actuate a gastric resident device made from a shape-memory alloy called Nitinol. Finally, we highlight the advantages and future directions for leveraging this novel in situ heat generation method beyond the showcased example., Competing Interests: The authors declare the following competing financial interest(s): The authors declare filing of provisional patent application US Patent application No. 63/331521 describing part of the system reported here. Complete details of all relationships for profit and not for profit can be obtained by emailing G.T., (© 2023 The Authors. Published by American Chemical Society.)