Revealing the critical thermodynamic parameters determining the glass formation of substances is of great significance for understanding the glass transition and guiding the composition design of glass‐forming materials. Nevertheless, the direct access to glass‐forming ability (GFA) by thermodynamics for various substances remains to be substantiated. The strategy to seek the fundamental properties of glass formation is explored several decades ago, as pioneered by Angell, arguing that the GFA in isomeric xylenes depends on the low lattice energy manifested by the low melting point. Here, an in‐depth study is advanced using two more isomeric systems. Surprisingly, the results do not constantly support the reported relationship between the melting point and glass formation among isomeric molecules. Instead, molecules with enhanced glass formability are featured by the properties of low melting entropy without exception. Comprehensive studies of isomeric molecules find that the low melting entropy is roughly accompanied by the low melting point, explaining the apparent link between melting point and glass formation. Progressively, the viscosity measurements of the isomers uncover a strong dependence of the melting viscosity on melting entropy. These results emphasize the significance of the melting entropy in governing the glass formability of substances.