Flexible electronics plays important roles in many research fields, including but not limited to biomedicine, energy devices, robotics, and virtual/augmented reality. Multilayer configurations stack different flexible electronic components in a vertical layer-by-layer format, thereby providing multimodality, high density and many other advanced features. This review picks representative works of multilayer flexible electronics in recent years, with a focus on introducing the manufacturing approaches and applications. Specifically, schemes in constructing multilayer flexible electronic systems mainly involve direct multilayer microfabrication and layer-by-layer transfer printing, with additional options in forming three-dimensional geometries and multilayer interconnections; applications of multilayer flexible electronic systems span from optoelectronic and robotics to biomedicine and energy devices. As a concluding remark, this article summarizes the challenges and prospects of multilayer flexible electronics.