Aiming at the problem of excessive swelling of conventional microspheres for oilfield use, a novel amphiphilic polymerizable crosslinker (AE) was synthesized by quaternary ammonium modification of an unstable crosslinker (AE) using acrylamide, 2-acrylamido-2-methylpropanesulfonic acid as the monomers, N,N’-methylene bisacrylamide as the stabilizing crosslinker, ammonium peroxysulfate and sodium bisulfite as the initiator, and water as the solvent by using a reversed microemulsion method. Double-networked nanomicrospheres were prepared. The preparation conditions of the microspheres were optimized by the surface response method, focusing on the effects of the initiator addition and reaction temperature, and total crosslinker addition on the formation of nanomicrospheres. The samples were characterized by FTIR, TGA, laser particle sizer, and SEM to evaluate the retarded expansion performance and the modulation drive performance. The results showed that the optimal conditions for the preparation of microspheres were m(oil phase):m(water phase) = 3:2, stirring speed of 550 r/min, total crosslinking agent dosage of 0.6% (based on the total mass of monomers, hereinafter the same), initiator dosage of 0.30%, reaction temperature of 45 °C, and reaction time of 4 h. Compared with the conventional polymer microsphere PAM, PAE was slow-expanded for 45 d at 60 °C, and the expansion multiplier was about 16 times, with slow-expansion characteristics; the blocking rate of PAE reached 98.3%, the oil repulsion rate was 73.11%, and the increase in the recovery rate could be up to 11.23%. In this paper, a new type of nanomicrosphere material is investigated to realize the efficient implementation of oil field conditioning and driving.