Despite its widespread occurrence in nature and broad application in industrial practice, nucleation of crystalline materials remains largely unpredictable and therefore difficult to control. In this work, we demonstrate a new method to control nucleation with polymer microgels by tuning their microstructure to vary systematically the degree of nanoscopic confinement and its effects on nucleation. We find that the polymer microstructure has a significant impact on nucleation kinetics. Moreover, there exists an optimum polymer mesh size at which the rate of nucleation is dramatically enhanced, the degree to which depends on the extent of polymer solute interactions. With easily tunable microstructure and chemistry, polymer microgels offer a promising approach for the rational design of materials for controlling nucleation from solution.