Display omitted •Design methods of co-immobilized multi-enzymes are summarized.•There will be great demand on applications of multi-enzyme system.•The challenges and future prospective of multi-enzyme immobilization are discussed. Enzyme catalysis has been attracting increasing interest in the past twenty years. Nevertheless, most reports concerning enzyme catalysis have been carried out using single enzymes. Recent years, multiple enzyme cascade reactions have a significant role for the production of many compounds at an industrial level because they permit to perform very complex reactions. Especially, the development of coimmobilized multienzymatic systems is increasingly driven by economic and environmental constraints that provide an impetus to develop alternatives to conventional multistep synthetic methods. Up to now, process optimization and novel strategies of coimmobilized multienzymatic systems hardly have been reviewed. In this review, we focus on some recent novel techniques in preparing co-immobilized multienzymatic systems and the up-to-date advances in the application of multienzymatic systems. Moreover, we also discuss the improvements that co-immobilization multienzymatic systems offer enzymes such as reusability, catalytic activity, and stability.