The development of flexible pressure sensors has attracted increasing research interest for potential applications such as wearable electronic skins and human healthcare monitoring. Herein, we demonstrated a piezoresistive pressure sensor based on AgNWs-coated hybrid architecture consisting of mesoscaled dome and microscaled pillar arrays. We experimentally showed that the key three-dimensional component for a pressure sensor can be conveniently acquired using a vacuum application during the spin-coating process instead of a sophisticated and expensive approach. The demonstrated hybrid structure exhibits dramatically improved sensing capability when compared with the conventional one-fold dome-based counterpart in terms of the sensitivity and detectable pressure range. The optimized sensing performance, by integrating D1000 dome and D50P100 MPA, reaches a superior sensitivity of 128.29 kPa (0-200 Pa), 1.28 kPa (0.2-10 kPa), and 0.26 kPa (10-80 kPa) and a detection limit of 2.5 Pa with excellent durability. As a proof-of-concept, the pressure sensor based on the hybrid configuration was demonstrated as a versatile platform to accurately monitor different kinds of physical signals or pressure sources, e.g., wrist pulse, voice vibration, finger bending/touching, gas flow, as well as address spatial loading. We believe that the proposed architecture and developed methodology can be promising for future applications including flexible electronic devices, artificial skins, and interactive robotics.