The current work investigates the combined effects of substrate wettability patterns and preset surfactant distributions on the dynamics and rupture of thin liquid films. The configuration considered here is a liquid film with a free surface above, and bounded below by a solid substrate with alternate zones of less and more wettable areas. This wettability-based patterning triggers an instability of the liquid film, caused by the outward flow from less to more wettable regions at the liquid–substrate interface. Introducing surfactants in the liquid film also affects the interfacial dynamics through Marangoni flow at the air–liquid interface. A variety of distribution functions are used as initial conditions for the surfactant concentration, to suitably modify the final configuration of a flat film. A set of two evolution equations for the film height and surfactant concentration are developed as partial differential equations to be solved numerically and simultaneously. Results indicate that the interplay between substrate wettability and surfactant distributions may significantly alter the ruptured film configurations. Typical scenarios include multiple near-rupture events in place of a single rupture, asymmetry in the ruptured film profile, and reversal of flow leading to film rupture on a more wettable region of the substrate. The results also provide insights into the dependence of rupture time scales on the inherent length scales in the problem, such as the pattern feature widths and the size of the surfactant-depleted zones. © 2019 Elsevier Masson SAS