Surfaces may appear to be flat and homogeneous by human observation, but upon closer inspection at sub-micron length scales they can reveal a rich and quite varied chemistry and topology which impart sometimes unexpected behaviors, such as the self-cleaning lotus leaf, or insects which can walk on water. There exist many theoretical equations which often provide reliable estimates of macroscopic properties such as surface energy, fluid contact angle, or individual forces contributing to adhesion between surfaces. However, because many of these theories rely on assumptions about ideal geometry and chemical homogeneity, they may not accurately capture the details of wetting and adhesive behavior at sub-micron length scales. For applications which rely on nanoscale features, such as micro-fluidics, chemically active laboratory or consumer product surfaces, or understanding how the aforementioned biological systems work, those local heterogeneities are key to understanding and manipulating interfacial behavior. By applying molecular dynamics simulations to ideal mesoscopic surfaces with features designed to prevent wetting, and atomistic amorphous surfaces in various environments, we studied interfacial behavior for systems of interest. Using rareevent sampling techniques we quantified the thermodynamics and kinetics of the wetting transition to show that re-entrant roughness features can be constructed to increase the transition energy barrier for moderately phillic fluids, but as the in- trinsic contact angle of that fluid decreases, representing a decrease in fluid surface tension, the chemistry quickly dominates the free energy landscape, resulting in full wetting of the idealized surface despite the topological transition energy barrier. The wetting transition state is shown to depend on fluctuations in the fluid interface, a condition which is not considered in most macroscopic treatments. At the atomistic level, we performed adhesion energy simulations on an amorphous glass surface in dry and humid conditions. Our results indicate that the type of surface hydroxyl can impact how strongly the surface will adhere to another similar surface, depending on both potential of interaction and steric factors within the bulk. Specifically, addition of B-hydroxyl groups reduces the adhesion between surfaces as compared to a pure silica surface. Additionally, conditions of low relative humidity show lower adhesion than high humidity, as a liquid bridge is unable to form below about 10% RH. Interfacial behavior of solid surfaces at the sub-micron scale is a result of complex interplay between local chemistry and topology, which change the functional response of those surfaces in ways that may not be predicted by macroscale equations. Molecular simulations can elucidate the impact of local conditions and lead to methods for controlling surface performance.