The performance of a simple multiscale approach to rapidly screen the second-order nonlinear optical (NLO) susceptibilities [χ(2)] as well as the refractive indices of organic crystals solely from the knowledge of their crystal structure is demonstrated. The method combines first principles calculations of the molecular properties with a classical electrostatic interactions scheme to account for the crystal environment effects. The calculated values reproduce closely the measured χ(2) response for 10 organic crystals, including ionic crystalline salts, covering a χ(2) range from 10 to 600 pm V–1. The agreement between calculations and measurements is also excellent in the case of the refractive indices. Moreover, the method allows to analyze the relationship between the macroscopic responses [χ(2)] and the molecular first hyperpolarizabilities, highlighting the effects of crystal packing and chromophore density as well as the role played by the crystal dressing field.