Multifunctional hybrid silica nanoparticles with a fluorescent core and tunable organic or polymeric shell can easily be prepared by a sol-gel process followed by 1,3 dipolar cycloaddition (CuAAC) in the same reverse quaternary W/O microemulsion. Compared to a classical multistep process, this one-pot synthesis reduces greatly the number of purification steps and avoids aggregation phenomena. The confinement of reactants inside the micellar system gives rise to a noticeable increase of the CuAAC reaction rate. In addition, using simultaneously two different substrates for CuAAC on silica allows us to obtain directly multifunctional hybrid nanoparticles displaying a double grafting without any separation or purification steps except the final recovery by centrifugation, which opens the door to a tunable coating of the nanoparticles. Particularly, the hydrophilic-lipophilic balance of the coating can be adjusted by implementing the pertinent MPEG:dodecyl azide ratio. As an application, the great versatility of this strategy has been proved by the one-pot synthesis of fluorescent silica nanoparticles with a PEG coating and encapsulating silver clusters.