We review the state-of-the-art in the molecular design and processing of nanomaterials at the extreme limits of molecular-scale confinement. A particular focus is provided on unique mechanical and electrical behavior that can be achieved in the limit of such intimate molecular mixing. We show that molecular hybrids can have marked asymmetric elastic and thermal expansion properties that are inherently related to terminal chemical groups in confinement. We describe a new nanoscale design principle using hyperconnected molecular architectures to achieve remarkable mechanical properties controlled by designing connectivity into the intrinsic molecular structure in innovative ways. We probe the mechanical and fracture properties of hybrids in the extreme limits of molecular confinement, where a stiff inorganic matrix phase confines polymer chains to dimensions far smaller than their bulk radius of gyration. Finally, we demonstrate the synthesis of 1D core-shell nanowires that have electrically conducting copper cores and insulating shells. Nanowires are synthesized via a facile solution process leveraging the strong chemical interaction between organothiol molecular precursors and copper. We use molecular dynamic and density functional theory computations together with atomic resolution characterization to reveal the molecular structure, and electrochemical impedance spectroscopy to characterize the electrical properties.