<p>Shell structures characterized by instability and negative stiffness are suitable for adoption in the design of mechanical metamaterials for energy absorption and shock isolation. However, the negative stiffness behavior of simple spherical shells faces significant challenges in practical applications due to constraints in geometric dimensions and boundary conditions. Here, a spherical shell with a small cylindrical connector at its dome is designed to exhibit negative stiffness behavior under predetermined fixed conditions. In experiments, we systematically evaluated 3D-printed thermoplastic polyurethane (TPU) through a series of tension–compression tests, confirming its exceptional performance in large deformation, stress concentration, and resisting failure under cyclic loading. We found that the resting time of the samples had a greater impact on the mechanical response than extrusion temperature and layer height. Compared to specimens with a resting time of 1&#xa0;h, those rested for 1&#xa0;month exhibited increases in tensile and compressive moduli of up to 27% and 15%, respectively. Finite element analysis (FEA) was employed for parametric studies to delineate the design boundary of the spherical shells between positive and negative stiffness. The data obtained from FEA were fitted using a quadratic surface model, thereby laying an empirical foundation for the design of programmable metamaterials. The unit was experimentally validated. To enhance the accuracy and reliability of the experimental results, we conducted a systematic analysis of discrepancy sources and found that the main discrepancy arises from manufacturing variability, such as inherent defects. The design and manufacturing methodology demonstrate considerable potential for application in mechanical metamaterials.</p>