The precise regulation of thermal expansion is a crucial and challenging issue with significant industrial and technological implications. We propose a Charge interaction index (CII) to relate thermal expansion to chemical composition. Using A2M3O12 compounds as a case study, we show the validity of this parameter through experimental verification. First, the charge density, potential well curves, and Grüneisen parameters of A2Mo3O12 (where A = Al, Sc, and Y) were extracted by first-principles calculations. These calculations revealed that the CII value is directly correlated with the transverse thermal vibrations of bridging O atoms and, in turn, with the low-frequency phonon modes exhibiting negative Grüneisen parameters. Three representative component designs, Sc1.6(MgTi)0.2Mo3O12, In2Mo2.5W0.5O12, and (Al0.2Sc0.2Fe0.2Ga0.2Cr0.2)2W3O12, were synthetized. As predicted, synchrotron XRD as a function of temperature showed that In2Mo2.5W0.5O12, which has the minimum CII value, exhibits NTE behavior, while (Al0.2Sc0.2Fe0.2Ga0.2Cr0.2)2W3O12, with the maximum CII value, displays positive thermal expansion (PTE). This work provides a simple and effective approach for controlling thermal expansion in open-framework materials through the CII idea.