With the development of 5th-generation wireless technology (5G), more and more attention has been focused on the flexible wearable sensors with high sensitivity and high reliability in the coming smart city. In this article, the sensitization mechanism of microstructures in pressure sensors and the reliability of sensitive layer were studied based on the theory and numerical calculation. The pressure sensing principles of capacitive sensors and piezoresistive sensors were introduced theoretically. Five different micro patterns under external pressure were investigated by finite element (FE) method to obtain the optimal structures of capacitive sensors and piezoresistive sensors, which were consistent with the theoretical analysis results. The analysis of interface reliability for a piezoresistive sensor showed that the sensor structure buckled during compression. The wavelengths of buckling were linearly proportional to the thickness of the piezoresistive film layer. In addition, the maximum stress appeared at the interface between the valley and the peak position, resulting in the risk of interface delamination. Once the delamination buckling instability occurred, the decrease of interface stiffness would lead to a large deformation at the first buckling point. This work can provide theoretical guidance for the design of highly sensitive and reliable 5G flexible wearable sensors.