Vibrant research has demonstrated that the layer-by-layer (LBL) approach can achieve a preferable vertical microstructure; however, the lack of precise control over vertical composition and molecular organization remains. Herein, we demonstrated a guest polymer-tailored LBL (GPT-LBL) strategy to achieve the p-i-n microstructure constructed by in situ monitoring pre-aggregation behaviors of non-fullerene acceptors. This superior structure with built-in interpenetrating networks alleviates the trap density states and the energy loss, improves hole transfer dynamics, and balances the charge transport, thus maximizing open-circuit voltage (V_OC), short-circuit current density (J_SC), and fill factor (FF) simultaneously. Consequently, a highly efficient GPT-LBL organic solar cell (OSC) with a power conversion efficiency (PCE) of 19.41% (certified 19.0%) was achieved. Noticeably, the large-area (1.03 cm²) device for GPT-LBL OSCs yields a satisfactory PCE of 17.52% in open-air blade coating, which is one of the best values in green-solvent-processed OSCs. The insights for p-i-n structure will give implications for the device engineering and photo physics understanding, offering an effective way to enable efficient, stable, and scalable OSCs.