Organic solvent forward osmosis (OSFO) process is a potential method for separating pharmaceuticals from organic solvents due to its low energy consumption and without external pressure requirements. However, OSFO process is limited in practical application due to low solvent flux. Here we reported the use of organic solvent pressure-assisted osmosis (OSPAO) process, which is a novel OSFO operation with increases a driving force (≤1 bar) in the same direction as solvent flow, enhancing solvent flux by combining osmotic pressure driving force with external hydraulic pressure. This work highlights a thermal facilitated simultaneous phase-inversion and crosslinking (T-SIM) strategy, which facilitates crosslinking degree and reduces preparation time and multi-step operations of solvent-resistant polyimide (PI) substrates. The temperature and extended time during the T-SIM strategy can more effectively controlling the physicochemical property and surface pore structures of solvent-resistant PI substrates. The morphological and physicochemical changes of the solvent-resistant PI substrates were observed by SEM, AFM, XPS, TG, contact angle and ATR-FTIR spectroscopy. Polyamide (PA) membranes were produced on the solvent-resistant PI substrates using an interfacial polymerization (IP) process, which led to the creation of defect-free PA layers with “ridge-and-valley” patterns. The methanol flux of 9.65 L m-2h−1 (LMH) and oxytetracycline (OTC) rejection of > 91% under the organic solvent nanofiltration test were achieved for the optimized T-SIM120 membrane, while the ethanol flux of 7.24 LMH and OTC rejection higher than 97% were observed under the OSPAO test. Additionally, DMF activation improved membrane permeance, the maximum ethanol flux of the T-SIM120 membrane after 2 h DMF activation reached 8.27 LMH under 1 bar during the OSPAO process and OTC rejection > 97%. The OSPAO process in this work demonstrated higher ethanol flux compared to the OSN process, lower Js/Je and enhanced OTC rejection compared to the OSFO process. Then the unique characteristic makes OSPAO process a desirable technology for solvent recovery in the pharmaceutical industry.