To overcome these limitations, in this study we used metadynamics simulations to gain atomistic insight into the process of assembly of these capsules developing a general simulation protocol. This allowed us to shed light on the fundamental thermodynamic, structural, and mechanistic aspects that influence the stability and equilibrium properties of these capsules. Such an approach could be easily transferred to the characterization of other complex assembly equilibria beyond supramolecular systems like biological compartmentalization. We found out that assembly is a thermodynamically favored process for both resorcinarene and pyrogallolarene capsules. Surprisingly, the mechanism that leads to assembly is radically different for the two types of calixarenes despite the little structural difference between their monomeric units. The origin of this large discrepancy in the process appears to be largely influenced by the ability of forming intermolecular hydrogen bonds among monomers, which in the case of resorcinarene is further assisted by the co-adjuvant role played by stoichiometric quantities of water present in the simulation box. In fact, the particular arrangement of the phenolic OH functionalities in the calixarene units determines the possibility of forming favorable dimer structures only in the case of resorcinarene. However, the presence of an additional OH group in pyrogallolarenes impedes the formation of intermolecular hydrogen bonds among monomers, and dimers can only form via less stable dipole-dipole interactions.