Humidity control is relevant to many processes in buildings and manufacturing and is responsible for over 600 million tons of CO2 annually. As such, desiccants that can efficiently remove moisture from air can greatly reduce emissions. A new class of desiccant materials, thermo‐responsive desiccants, has been of increased interest in the literature. These materials are generally based on thermo‐responsive polymers and exhibit a temperature‐dependent isotherm, an attribute that is small in traditional desiccants. In this work, seven key parameters needed to create an effective thermo‐responsive polymer desiccant are identified using a combination of modeling and experimental data. It is found that more thermo‐responsiveness is not necessarily better for energy efficiency, and that an optimal, “medium” value is desired. Additionally, polymer composition and architecture play key roles in adjusting the seven key parameters. Finally, based on findings from both modeling and experimental work, guidelines on synthesizing future thermo‐responsive polymer desiccants are presented.