Emergent mechanics of musculoskeletal extremities (surface indentation stiffness and tissue deformation characteristics) depend on the underlying composition and mechanics of each soft tissue layer (i.e. skin, fat, and muscle). Limited experimental studies have been performed to explore the layer specific relationships that contribute to the surface indentation response. The goal of this study was to examine through statistical modeling how the soft tissue architecture contributed to the aggregate mechanical surface response across 8 different sites of the upper and lower extremities. A publicly available dataset was used to examine the relationship of soft tissue thickness (fat and muscle) to bulk tissue surface compliance. Models required only initial tissue layer thicknesses, making them usable in the future with only a static ultrasound image. Two physics inspired models (series of linear springs), which allowed reduced statistical representations (combined locations and location specific), were explored to determine the best predictability of surface compliance and later individual layer deformations. When considering the predictability of the experimental surface compliance, the physics inspired combined locations model showed an improvement over the location specific model (percent difference of 25.4 +/- 27.9% and 29.7 +/- 31.8% for the combined locations and location specific models, respectively). While the statistical models presented in this study show that tissue compliance relies on the individual layer thicknesses, it is clear that there are other variables that need to be accounted for to improve the model. In addition, the individual layer deformations of fat and muscle tissues can be predicted reasonably well with the physics inspired models, however additional parameters may improve the robustness of the model outcomes, specifically in regard to capturing subject specificity.