Architected metamaterials derive their exceptional mechanical performance from precisely tailored topologies, enabling access to regions of materials selection charts unattainable by conventional materials. While substantial advances have been achieved at micro-, meso-, and macroscales, further improvements are increasingly constrained, motivating exploration of nanoscale architected materials, where surface and size effects dominate. Here, we resort to molecular dynamics simulations to systematically explore the mechanical response of nickel-based nano-architected metamaterials. By varying topology, relative density, crystallinity, and grain size, we demonstrate the broad tunability of elastic moduli, strength, and Poisson’s ratio enabled by the rational design of underlying nano-architecture. Notably, the proposed nano-architected metamaterials outperform most previously reported architected materials at comparable densities, highlighting the effectiveness of nanoscale topology-driven design. Atomistic analyses reveal that nanoscale free surfaces promote dislocation nucleation while inhibiting dislocation propagation, leading to flow stresses exceeding those of bulk counterparts. To bridge length scales and draw inspiration from crystallography, we further design and 3D print hierarchical polymeric metamaterials and experimentally characterize their mechanical behavior. Despite being fabricated from an intrinsically brittle polymer, these structures exhibit topology-dependent stiffness and strength, alongside ductile plastic deformation and enhanced toughness, attributable to their hierarchical architectures. Together, this work establishes a crystallography-inspired architectural design paradigm for mechanical metamaterials and imparts scalable design guidelines for achieving lightweight, mechanically efficient structures across multiple length scales.