A computationally affordable approach, based on quasi-harmonic lattice dynamics, is presented for the quantum-mechanical calculation of thermoelastic moduli of flexible, stimuli-responsive, organic crystals. The methodology relies on the simultaneous description of structural changes induced by thermal expansion and strain. The complete thermoelastic response of the mechanically flexible metal–organic copper(II) acetylacetonate crystal is determined and discussed in the temperature range 0–300 K. The elastic moduli do not just shrink with temperature but they do so anisotropically. The present results clearly indicate the need for an explicit account of thermal effects in the simulation of mechanical properties of elastically flexible organic materials. Indeed, predictions from standard static calculations on this flexible metal–organic crystal are off by up to 100%.