We here report an efficient and enhanced fluorescence energy transfer system between confined quantum dots (QDs) by entrapping CdTe into the mesoporous silica shell (CdTe@SiO2) as donors and gold nanoparticles (AuNPs) as acceptors. At pH 6.50, the CdTe@SiO2–AuNPs assemblies coalesce to form larger clusters due to charge neutralization, leading to the fluorescence quenching of CdTe@SiO2 as a result of energy transfer. As compared with the energy transfer system between unconfined CdTe and AuNPs, the maximum fluorescence quenching efficiency of the proposed system is improved by about 27.0%, and the quenching constant, K sv, is increased by about 2.4-fold. The enhanced quenching effect largely turns off the fluorescence of CdTe@SiO2 and provides an optimal “off-state” for sensitive “turn-on” assay. In the present study, upon addition of melamine, the weak fluorescence system of CdTe@SiO2–AuNPs is enhanced due to the strong interactions between the amino group of melamine and the gold nanoparticles via covalent bond, leading to the release of AuNPs from the surfaces of CdTe@SiO2; thus, its fluorescence is restored. A “turn-on” fluorimetric method for the detection of melamine is proposed based on the restored fluorescence of the system. Under the optimal conditions, the fluorescence enhanced efficiency shows a linear function against the melamine concentrations ranging from 7.5 × 10–9 to 3.5 × 10–7 M (i.e., 1.0–44 ppb). The analytical sensitivity is improved by about 50%, and the detection limit is decreased by 5.0-fold, as compared with the analytical results using the CdTe–AuNPs system. Moreover, the proposed method was successfully applied to the determination of melamine in real samples with excellent recoveries in the range from 97.4 to 104.1%. Such a fluorescence energy transfer system between confined QDs and AuNPs may pave a new way for designing chemo/biosensing.