Previously derived approximate analytical relations for the activity coefficient of each solute in a mixture of up to three spherical solutes in a highly nonideal solution interacting via square well potentials of mean force (Hoppe, T.; Minton, A. P. J Phys Chem B. 2016, 120, 1186611872) were used to explore the effect of heterogeneity in volume occupancy and intermolecular interactions upon prototypical schemes representing solubility, partitioning, conformational isomerization, and self-association in crowded solutions. Results generally indicate that all of the equilibria explored are exquisitely sensitive to variations in both volume occupancy and intermolecular interaction and have important implications for the design and execution of more detailed simulations of complex media.