Inspiration from natural designs offers opportunities to develop novel functional materials having unique properties. An active area of research in this field is the construction of anisotropic nanostructured surfaces, which exhibit direction dependent wetting behavior. Here, we demonstrated the effects of surface chemistry and morphology on the directional wetting phenomenon. The nanofilms having directionality were fabricated at varying tilt angles (beta) via oblique angle deposition (OAD) technique. The chemical modifications of engineered nanofilms were then carried out by using thiol molecules having different end groups (i.e., -CF3, -CH3, and -phenyl). We found that surface morphology and chemistry are extremely important parameters in the control of directional wetting. By this way, it was possible to manipulate the movement of a water droplet on the nanostructured surfaces. Such a control would have a great impact for several technological applications involving catalysis, tissue engineering, and biosensors.