It is important that we understand the physical, chemical, and biological mechanisms that govern the interaction between nanoparticles (NPs) and heterogeneous cellular surfaces because of the possible cytotoxicity of engineered nanomaterials. In this study, we investigated the lateral localization of nano/microparticles within a biomimetic heterogeneous membrane interface using cell-sized two-phase liposomes. We found that lateral heterogeneity in the membrane mediates the partitioning of nano/microparticles in a size-dependent manner: small particles with a diameter of <= 200 nm were localized in an ordered phase, whereas large particles preferred a fluidic disordered phase. This partitioning behavior was verified by temperature-controlled membrane miscibility transition and laser-trapping of associated particles. In terms of the membrane elastic energy, we present a physical model that explains this localization preference of nano/microparticles. The calculated threshold diameter of particles that separates the particle-partitioning phase was 260 nm, which is in close agreement with our observation (200 nm). These findings may lead to a better understanding of the basic mechanisms that underlie the association of nanomaterials within a cell surface.