The vagina helps support the bladder, urethra, uterus, and rectum. A lack of support leads to pelvic organ prolapse, and vaginal delivery is a prevalent risk factor; however, there is little research on vaginal biomechanical properties. Despite numerous complications, clinical practice involves surgical repair with synthetic meshes. Complications can be partially attributed to our lack of knowledge regarding the mesh-tissue complex (MTC) after implantation. However, it is difficult to perform rigorous studies without utilizing animal models. Therefore, we evaluated how parity affected the mechanical properties of vaginal tissue in three animal models: rodent, sheep, and non-human primate (NHP) to compare their mechanically properties to parous women who typically undergo prolapse surgery. Parity negatively impacted the mechanical properties of the vagina in NHP, which were biomechanically similar to parous women, making it a suitable model for studying the effects of mesh implantation. Second, we examined the textile and structural properties of commonly used meshes (Gynemesh, UltraPro, SmartMesh, Novasilk, and Polyform) utilizing uniaxial and ball-burst tests. These meshes had significantly different porosity and structural properties. To investigate the host response, three meshes were implanted into the abdominal wall of the rodent and NHP, and on the vagina in the NHP. The MTC was removed, and the tissue contribution was calculated. We did not observe notable changes in the tissue properties following mesh implantation in the rodent; however, implantation of the stiffest mesh (Gynemesh) in the NHP resulted in an exhibition of a stress shielding response manifested by inferior biomechanical properties of the abdominal and vaginal tissues. Less stiff meshes (UltraPro and SmartMesh) resulted in preservation of tissue properties. To gain insight into how mesh properties affect the tissue contribution, we began developing a finite element model. Utilizing the co-rotational theory with a fiber-recruitment stress-strain relationship, we could describe the behavior of SmartMesh and UltraPro. While an in-depth characterization of these meshes revealed multiple fiber populations, further development of modeling may be instrumental in closing the current knowledge gap. Ultimately, understanding the mesh-tissue interaction will improve clinical outcomes by identifying mesh properties that are essential for providing structural support while maintaining tissue integrity