Heterogeneous junctions extensively exist in electronic and photovoltaic devices. Due to essential differences, the contacts of heterogeneous junctions are imperfect with structural discontinuity and chemical inconsistency, which have negative impacts on the mechanical, electrical, and thermal properties of devices. To improve the heterogeneous interactions, surface/interfacial modification approaches are developed in which molecular assembly engineering appears to be a promising strategy. Versatile functionalities can be accomplished by smart arrangement and design of the functional groups and geometry of the organic molecular layers. Specific functionality can also be maximized by well organization of the grafting orientation of molecules at the heterogeneous contacts. This article comprehensively reviews the approaches of molecular assembly engineering employed in the construction of the heterogeneous junctions to improve their mechanical, electrical, and thermal properties. Following the introduction of molecular assembly engineering at the target surface/interface, examples are introduced to show the efficacy of molecular assembly engineering on the interfacial adhesion, atomic interdiffusion, dielectric nature, charge injection and recombination, and thermoelectric property in electronic and photovoltaic devices.