Advances in enhanced oil recovery (EOR) require quantification of surface wetting phenomena on the nanometer scale under well controlled conditions. We introduce a novel measurement platform that enables optical microscopy and atomic force microscopy within a dedicated, optically transparent analysis device. The measurement entails the deposition and characterization of extremely small amounts of liquids having volumes on the order of 10 attoliters (10–17liter). The analyzed liquids are located at a well-characterized test surface that is customizable to match the specifics of the experiment, e.g. by surface patterning or surface functionalization. We present initial experimental and simulation results that demonstrate that it is possible to map within the device individual, spatially isolated oil droplets with diameters well below the micrometer scale having heights of several tens of nanometers only. The combined analysis of high-resolution optical and topographical data reveals how oil droplet shape and surface wetting behavior are determined by the properties of the liquid and local properties of the test surface, such as surface roughness. Future applications of the measurement platform in the domain of oil recovery include screening of EOR chemicals and verification of advanced molecular dynamics models of liquid-solid interactions.