<p>Wrinkling of film/substrate system is commonly observed in nature, and has recently gained significant research interest in various industrial sectors such as flexible electronics. However, most studies have treated both the film and the substrate as homogeneous materials, and the understanding toward the wrinkling of heterogeneous film/substrate systems has remained largely unexplored. In this study, we present a systematic study on the wrinkling of a heterogeneous thin film over a liquid substrate, with a particular focus on the influence of the microstructures on the critical and post-wrinkling behavior of the system, using both analytic method and numerical simulation. When the critical wavelength is much larger than the characteristic length scale of material heterogeneity, the wrinkling behavior is dictated by the homogenized properties of the film; yet when the two scales are close to each other, the material heterogeneity has a strong influence on the critical wavelength. Furthermore, under such scenario, new post-wrinkling profiles can also be observed, which is a function of both the geometric and mechanical properties of the film. Such observation not only provides insights into wrinkling behavior of heterogeneous film/substrate systems, but can also potentially inspire new ways of controlling the wrinkling profiles.</p>