Integration of multiple incompatible catalysts in one continuous-flow reaction system is of paramount significance for green synthetic chemistry. Here we develop a continuous-flow cascade catalytic system by co-packing micrometre-sized Pickering emulsion droplets and solid microspheres in a column reactor. This co-packed system can not only provide the optimum microenvironments for each incompatible catalyst but also enables them to work synergistically through directional transfer of reaction intermediates. The success of the concept is based on a phenomenon found here, namely coexistence of Pickering emulsion droplets and solid microspheres without droplet disruption even under flow and high pressure due to specific interfacial effects. As proof of concept, two chemoenzymatic cascade reactions for synthesis of chiral cyanohydrins and chiral esters were examined; both these reactions exhibited 7-fold to 77-fold enhanced catalysis efficiency compared with their batch reactions, 99% enantioselectivity and long-term operational stability (240 h).