A novel patterned-void structure is developed to improve the fatigue life compared with conventional circular cooling holes typically used in gas turbine components exposed to high temperatures. The distinctive S-shape of the voids and their specific arrangement enable manipulation of the structure's macroscopic stiffness and Poisson's ratio. An investigation of the isothermal and thermomechanical fatigue (TMF) properties of the proposed structure is carried out in strain-controlled conditions. The testing is performed on tubular specimens machined from a Nickel-based superalloy commonly used in gas turbine combustion systems (HAYNES 230®). The isothermal fatigue tests, performed at 300 °C, 600 °C, and 800 °C, demonstrated an increase in crack-initiation life of the proposed structure by a factor of up to 28 compared with the standard circular holes. The thermomechanical fatigue tests, performed across temperature ranges 300 °C–750 °C and 300 °C–850 °C, and using in-phase (IP) and out-of-phase (OP) strain ratios, demonstrated an increase in crack-initiation life by a factor of up to 16. The life after crack initiation (crack-propagation mode) was also shown to be longer for the proposed structure, which is attributed to a crack-arresting behavior inherent to the structure.