As the depth of petroleum drilling increases, the strata environment becomes more complex. The efficiency and lifespan of Polycrystalline Diamond Compact (PDC) drill bits fail to meet current drilling demands. However, the structure and arrangement of PDC cutters are valuable determinants of drilling efficiency, although related research still has gaps and deficiencies. This study focuses on PDC cutters in axe, triangular prism, and circular forms. It establishes an inhomogeneous granite model based on the actual measurements of granite and verifies the accuracy of this model through uniaxial compression simulation. Finite element models of three types of cutters in various combination schemes are constructed to examine rock-breaking effects, with the best scheme optimized using Box-Behnken response surface methodology. The rock-breaking process of the optimal PDC drill bit layout has been compared to that of a single cutter bit. Field drilling has demonstrated the effectiveness of a mixed cutter arrangement. The results show that the inhomogeneous granite model can be trusted. The optimal arrangement involves axe cutters in the front row and an alternate arrangement of triangular prism cutters and axe cutters in the back row. The optimal lateral and longitudinal distances for the triangular cutters from the front row of axe cutters are 10 mm and 7 mm, respectively, while those for the back row of axe cutters from the front row are 10.06 mm and 7 mm, respectively. The ROP standard deviation in the drilling process of mixed cutter bits decreases by 53.06% and 43.08% compared to axe and triangular prism cutter bits, respectively. The drilling efficiency increases by 16.8% and 16.6%, respectively, demonstrating higher efficiency and stability. Field drilling results indicate that a mixed cutter bit increases efficiency by 23.5% compared to a bit with only triangular prism cutters. This study posits that research on the combination schemes and parameters of PDC cutters can significantly enhance drilling efficiency, thereby reducing the drilling cycle and costs.