The bottom-up assembly of biomimetic multicompartmentalized microreactors for use in continuous flow catalysis remains a grand challenge because of the structural instability or the absence of liquid microenvironments to host biocatalysts in the existing systems. Here, we address this challenge using a strategy that combines stepwise Pickering emulsification with interface-confined cross-linking. Our strategy allows for the fabrication of robust multicompartmentalized liquid-containing microreactors (MLMs), whose interior architectures can be exquisitely tuned in a bottom-up fashion. With this strategy, enzymes and metal catalysts can be separately confined in distinct subcompartments of MLMs for processing biocatalysis or chemo-enzymatic cascade reactions. As exemplified by the enzyme-catalyzed kinetic resolution of racemic alcohols, our systems exhibit a durability of 2000 h with 99% enantioselectivity. Another Pd-enzyme-cocatalyzed dynamic kinetic resolution of amines further demonstrates the versatility and long-term operational stability of our MLMs in continuous flow cascade catalysis. This study opens up a new way to design efficient biomimetic multicompartmental microreactors for practical applications.