The cohesive energy is a key quantity to determine the mechanical, physical, chemical, and electronic properties of materials. In this work, the interface effect on the cohesive energy of nanostructured materials and substrate-supported nanofilms is modeled free of adjustable parameters. The cohesive energy drops on lowering the grain size or thickness. However, this decrease is weak compared with nanocrystals, dependent on the interface energy size relative to the surface energy associated with the coordination imperfection. Based on this exploration, the interface effect on the thermal and electronic properties of melting point, thermal expansion coefficient, bandgap and core-level shift of nanostructured materials and/or nanofilms has also been modeled and discussed. Our theoretical predictions are validated by available experimental results.