Origami foldability, naturally realizable at the micro- and nanoscale, provides a pathway to enlarge the design space of mechanical metamaterials. In article number 2002229, Glaucio H. Paulino, Horacio D. Espinosa, Sridhar Krishnaswamy, and co-workers design and fabricate microscale 3D multifunctional origami-architected metamaterials and reveal their unique mechanical properties. Such metamaterials promise to influence various applications ranging from deployable medical devices to soft robotics in which size scalability, shape-morphability, and deployability coupled with directional mechanical property tunability are requisite attributes.