Thermal stability and thermodynamic properties of aluminum(III)-1,3,5-benzenetricarboxylate (Al-BTC) metal−organic frameworks (MOFs), including MIL-96, MIL-100, and MIL-110, have been investigated through a suite of calorimetric and X-ray techniques. In situ high-temperature X-ray diffraction (HT-XRD) and thermogravimetric analysis coupled with differential scanning calorimetry (TGA-DSC) revealed that these MOFs undergo thermal amorphization prior to ligand combustion. Thermal stabilities of Al-BTC MOFs follow the increasing order MIL-110 < MIL-96 < MIL-100, based on estimated amorphization temperatures. Their thermodynamic stabilities were directly measured by high-temperature drop combustion calorimetry. Normalized (per mole of Al) enthalpies of formation (ΔH* f ) of MIL-96, MIL-100, and MIL-110 from Al 2 O 3, H 3 BTC, and H 2 O (only Al 2 O 3 and H 3 BTC for MIL-100) were determined to be −56.9 ± 13.7, −36.2 ± 17.9, and 62.8 ± 11.6 kJ/mol•Al, respectively. Our results demonstrate that MIL-96 and MIL-100 are thermodynamically favorable, while MIL-110 is metastable, in agreement with thermal and hydrothermal stability trends. The enthalpic preferences of MIL-96 and MIL-100 may be attributed to their shared trinuclear μ 3 -oxo-bridged (Al 3 (μ 3 -O)) secondary building units (SBUs) promoting stabilization of Al polyhedra by the ligands within these frameworks, in comparison to the sterically strained Al 8 octamer cluster cores formed in MIL-110. Furthermore, similar ΔH* f of MIL-96 and MIL-100 explain their concurrent formation as physical mixtures often encountered during synthesis, implying the importance of kinetic factors that may facilitate the formation of Al-BTC framework isomers. More importantly, the normalized formation enthalpies of Al-BTC MOF isomers follow a negative correlation with the ratio of charged coordinated substituents to linkers (normalized per mole of Al within the MOF formula unit), with enthalpic preference given to systems with smaller (O 2− + OH − )/ligand ratios. This trend has been successfully extended to the previously measured ΔH* f of several Zn 4 O-based frameworks (e.g., MOF-5, MOF-5(DEF), MOF-177, UMCM-1), all of which have been found to be metastable with respect to their dense phases (ZnO, H 2 O, and ligands). The result suggests that carboxylate MOFs with higher metal coordination environments attain more enthalpic stabilization from the coordinated ligands. Thus, the formation of some lanthanide/actinide, transition metal, and main group carboxylate frameworks may be energetically more favored, which, however, requires further studies.