Microencapsulates with defined core-shell structures are of interest for applications, such as controlled release and encapsulation, because of the feasibility of fine-tuning individual functionalities of different parts. Here, we report a new approach for efficient and scalable production of such particles. Eudragit RS (a co-polymer of ethyl acrylate, methyl methacrylate, and a low content of methacrylic acid ester with quaternary ammonium groups) was used as the main shell component, with silica as the core component, formed upon a single-step spray-drying assembly. The method is capable of forming uniform core-shell particles from homogeneous precursors without the use of any organic solvents. Evaporation-induced self-assembly attained the phase separation among different components during drying, resulting in the core-shell spatial configuration, while precise control over particle uniformity was accomplished via a microfluidic jet spray dryer. Direct control over shell thickness can be achieved from the ratio of the core and shell ingredients in the precursors. A fluorescent compound, rhodamine B, is used as a highly water-soluble model component to investigate the controlled release properties of these microencapsulates, with the release behaviors shown to be significantly dependent upon their architectures.