Polymorphism, the phenomenon in which a compound crystallizes into more than one solid state crystal structure, has drawn attention in many industry fields, especially pharmaceuticals. In recent years, self-assembled monolayers (SAMs) have been used to study polymorph control because of their well-defined surface chemistry and structure. Furthermore, by tuning the substrate-crystal interface energy, potentially SAMs can promote the nucleation of polymorphs not accessible via solution methods. These advantages have led us to choose heterogeneous surface nucleation via SAMs as the primary means to study polymorph selection. In this work, we have examined multiple SAM chemistries on gold and silicon in the presence of various solvent systems to investigate their ability to influence the nucleation, crystal growth, and polymorph selection of a common drug, acetaminophen (ACM). We have found that both solvent and substrate work together to control crystal polymorph. On hydrophobic, methyl and phenyl terminated surfaces, using water, ethanol, or dioxane as solvent results in the monoclinic polymorph, while the orthorhombic polymorph is formed when using mixtures of water and dioxane. As a comparison to hydrophobic surfaces, hydroxyl terminated surfaces were investigated. In this case, using ethanol or dioxane as solvents results in orthorhombic polymorph selection, clearly different from crystallization results on hydrophobic surfaces. Interestingly, the methyl and phenyl terminated surfaces that promote the formation of the less thermodynamically stable orthorhombic form of ACM show (002) cleavage planes perpendicular to the substrate, while the -OH terminated surfaces induce that same polymorph with the (002) cleavage planes parallel to the substrate surface. We hypothesize that this selection is due to the energetic favorability of certain crystal facets interacting with the chemically distinct SAM surfaces.