In thiswork, a molecular dynamics simulationmethodwas introduced to compute the preassembled system of molecular imprinted polymers for sulfamethoxazole monomer. The results revealed that the ratio of sulfamethoxazole as template molecule to 3-aminopropyltriethoxysilane as functional monomer to tetraethylorthosilicate as cross-linker of 10: 10: 40 led to themost stable template-functionalmonomer cluster. Based on the result of computational simulation, CdTe@SiO2 core-shell imprinted polymers, a cadmium telluride quantum dots layer on the surface of aminofunctionalized SiO2, were synthesized as the fluorescent sensor. Then, a series of measures were used to characterize the structure and morphology to get optimal sensors. The concentration range was 5.0-30.0 mu mol/L between molecular imprinted polymers at CdTe at SiO2, and sulfamethoxazole of the fluorescence intensity. To further verify the reliability and accuracy of the fluorescent sensor, the application was successfully by analyzing sulfamethoxazole in pure milk and lake water. The results showed the recoveries were above 96.89% with a relative standard deviation of 1.25-5.45%, and the fluorescence sensor with selective recognition provides an alternative solution for the determination of sulfamethoxazole.