This study presents a multiscale evaluation of the nanomechanical behavior and structural organization of aponeurotic tissue under three clinically relevant conditions: normal, rejection-affected, and mesh-reinforced. Spatially resolved mechanical measurements were performed to assess local variations in the apparent elastic response, enabling the identification of distinct mechanical patterns associated with each condition. Normal tissue exhibited a relatively uniform mechanical profile, consistent with a well-organized structural architecture. In contrast, rejection-affected samples showed increased heterogeneity and loss of mechanical coherence, reflecting alterations in tissue integrity. Mesh-reinforced tissues revealed localized variations in stiffness, suggesting structural adaptation in response to the implanted material. The structural organization was further examined through orientation-sensitive analysis, highlighting a preferential alignment in normal tissue and a progressive disruption of this organization in pathological conditions. Partial reorganization was observed in the presence of the mesh. A key finding of this study is the relationship between local mechanical response and structural alignment, indicating that mechanically stiffer regions tend to coincide with preferentially oriented structures. These results emphasize the strong interplay between structure and mechanics and provide insight into the mechanisms governing aponeurotic tissue remodeling and biomaterial–tissue interaction.