Nerve guidance conduits (NGCs) are tubular tissue engineering scaffolds used for nerve regeneration. The poor mechanical properties and porosity have always compromised their performances for guiding and supporting axonal growth. Therefore, in order to improve the properties of NGCs, the computational design approach was adopted to investigate the effects of different NGC structural features on their various properties, and finally, design an ideal NGC with mechanical properties matching human nerves and high porosity and permeability. Three common NGC designs, namely hollow luminal, multichannel, and microgrooved, were chosen in this study. Simulations were conducted to study the mechanical properties and permeability. The results show that pore size is the most influential structural feature for NGC tensile modulus. Multichannel NGCs have higher mechanical strength but lower permeability compared to other designs. Square pores lead to higher permeability but lower mechanical strength than circular pores. The study finally selected an optimized hollow luminal NGC with a porosity of 71% and a tensile modulus of 8 MPa to achieve multiple design requirements. The use of computational design and optimization was shown to be promising in future NGC design and nerve tissue engineering research.