Computational prediction of thermodynamic components with computational methods has become increasingly routine in computer-aided drug design. Although there has been significant recent effort and improvements in the calculation of free energy, the prediction of enthalpy (and entropy) remains underexplored. Furthermore, there has been relatively little work reported so far that attempts to comparatively assess how well different force fields and water models perform in conjunction with each other. Here, we report a comprehensive assessment of force fields and water models using host-guest systems that mimic many features of protein-ligand systems. These systems are computationally inexpensive, possibly because of their small size compared to protein-ligand systems. We present absolute enthalpy calculations using the multibox approach on a set of 25 cucurbit[7]uril-guest pairs. Eight water models were considered (TIP3P, TIP4P, TIP4P-Ew, SPC, SPC/E, OPC, TIP5P, Bind3P), along with five force fields commonly used in the literature (GAFFv1, GAFFv2, CGenFF, Parsley, and SwissParam). We observe that host-guest binding enthalpies are strongly sensitive to the selection of force field and water model. In terms of water models, we find that TIP3P and its derivative Bind3P are the best performing models for this particular host-guest system. The performance is generally better for aliphatic compounds than for aromatic ones, suggesting that aromaticity remains a difficult property to include accurately in these simple force fields.