Objective To develop a three-dimensional (3D) comprehensive finite element (FE) foot model for studying the biomechanical effects of different parametrical designs with various foot orthoses, soft tissue stiffness and loading conditions. Methods Based on the accurate anatomical structures including the encapsulated soft tissue, ligaments and plantar fascia, and taking the nonlinear properties of material and foot contacting into consideration, a 3D FE mode of foot was developed. The reliability and validity of the FE model to quantify the biomechanical response of the foot and ankle under different simulated pathological, surgical and orthotic conditions were investigated. Results The FE analysis showed that such a custom-molded shape was more important for relieving of the plantar peak pressure than the stiffness of orthotic material as far as the design is concerned. Increasing soft tissue stiffness would lead to decrease the total contact area of the foot-support interface and then make the increases in plantar peak pressure of the bony prominences. Either reducing the stiffness of plantar fascia or surgical releases of the partial or the entire plantar fascia could decrease the arch height, increasing the strains of the plantar ligaments and intensifying the stresses in the midfoot and metatarsal bones. The FE predictions showed that both the increase of weight on the foot and achilles tendon loading resulted in an increase in tension of the plantar fascia with the latter showing a two-times larger straining effect. Conclusion The established FE model, which allowed prediction of plantar pressure distributions as well as the internal stress and strain of the bony and soft tissue structures, can be an effective tool to study different clinical questions and for footwear design.