Proteins perform many important biological functions while also avoiding fouling in a aqueous and crowded cellular environment. Their surfaces have evolved to be both chemically heterogeneous (containing nonpolar, polar, and charged groups) as well as hydrophilic. While nonpolar groups are known to induce hydrophobicity, surface heterogeneity has been found to enhance hydrophilicity and the resistance of non-specific adsorption of biomolecules. Yet, the exact relationship between the nature of heterogeneous surfaces and hydrophilicity is not fully understood. Therefore, protein surfaces offer a promising avenue of study to help elucidate this relationship. While many characterizations of protein surface hydrophilicity sum the individual hydrophilicity of amino acids, surface hydration of heterogeneous surfaces has been found to be highly context-dependent and thus non-additive. In this dissertation, we utilize molecular dynamics simulations to characterize the atomic-level, context-dependent hydrophilicity of protein surfaces to better understand how the chemical composition and surface patterning of protein surfaces enhance hydrophilicity. We demonstrate that charged moieties play a much more significant role in enhancing protein surface hydrophilicity than polar atoms do. In fact, we also demonstrate that chemical composition alone is insufficient to distinguish between hydrophilic and hydrophobic protein surface regions. Furthermore, we use these findings to develop protein-inspired design rules for heterogeneous non-fouling surfaces. The work in this dissertation could be used to inform the design of superhydrophilic materials as well as to elucidate the relationship between surface heterogeneity and hydrophilicity. Additionally, it could be used to not only better understand biomolecular interactions through a context-dependent characterization of protein hydrophilicity, but also to inform protein engineering.