As a new kind of water plugging and profile control agents, the polyacrylamide nano−microspheres have been experimentally applied and achieved satisfactory preliminary results in enhanced oil recovery, especially for low-permeability reservoirs. However, the larger swollen particle size and excessive hydrophilicity limit the effect at the oil−water interface. In order to further improve their profile control and flooding effect, the temperature-sensitive poly(N-isopropylacrylamide-acrylamide) nano−microspheres are prepared by inverse microemulsion polymerization. Based on the principle of conformation transition of PNIPAM triggered by simulated high temperature in reservoirs, the particle size and hydrophilicity of the microspheres are reduced, making it easier to reach the oil−water interface, reduce the oil−water interface tension, and enhance the structural disjoining pressure, which improves the spontaneous emulsification effect and removal effect of residual oil on rocks. The swelling properties, hydrophilicity, interfacial activity, and oil displacement properties of the nano−microspheres were also analyzed. The results show that the swelling ratio of the copolymerized nano−microspheres decreases to 1.5. At simulated reservoir temperature (65 °C), the water contact angle of copolymerized gel increases from 43 to 86°, indicating that its hydrophilicity decreases and shows a clear tendency to migrate to the water−oil interface. At 65 °C, 0.1 wt % PNIPAM-based microsphere emulsion (N3) reduces the oil−water interfacial tension from 17.8 to 0.9 mN m −1 . The microscopic oil displacement experiment shows that the recovery efficiency of our designed temperature-sensitive nano−microspheres emulsion is increased by 7%, which is higher than that of the PAM polymer nanosphere. The PNIPAM-based temperature-sensitive nano−microspheres that can function at the oil−water interface have a potential development prospect in low-permeability reservoirs.