To address the challenges of enhanced heterogeneity and severe water channeling in high water-cut oilfield reservoirs, a thermally sensitive modified polymer microspheres with both thermosensitive responsiveness and high retention capacity was developed to achieve deep selective water shutoff and improved oil recovery. A microfluidic in situ emulsion polymerization combined with PDA surface coating was employed as the bioinspired design strategy. By adjusting surfactant concentration and oil–water ratio, precise particle size matching was realized, and functional monomers were synergistically incorporated to construct a thermosensitive and salt–alkali adaptive composite structure. The microspheres were systematically characterized in terms of morphology, Zeta potential, FTIR, thermogravimetric performance, phase transition temperature, shear resistance, wettability, and interfacial tension. Results showed that the modified microspheres had a median particle size of approximately 800 nm, a higher absolute surface potential, and stable dispersion, with significantly enhanced thermal stability and shear resistance. At a concentration of 2wt%, the microspheres achieved optimal wettability and the lowest oil–water interfacial tension. Laboratory core flooding experiments at 120 °C demonstrated that injecting 0.5 PV of 2wt% microspheres reduced water cut by about 20% and increased recovery factor by about 15%. Field applications in three wells confirmed that, under high-temperature and high-salinity conditions, the microspheres significantly increased injection pressure, reduced water cut, and achieved a cumulative oil increment of 1.64×105 t. These findings indicate that the thermally sensitive modified polymer microspheres exhibit excellent thermal–salinity adaptability and targeted water shutoff efficiency, providing an effective technical approach for deep profile control and enhanced oil recovery in high-permeability reservoirs.