Molecular epitaxy-the process of growing a crystalline overlayer onto a substrate-at the two-dimensional (2D) material interfaces, opens new avenues toward the integration of 2D materials with a large variety of functional molecules. The emerging field of controlling molecular epitaxy on 2D materials interfaces toward functional heterostructures and novel optoelectronic devices clearly requires the understanding of the interplay between molecular interactions at the interfaces. In this article, we review the mechanisms governing molecular epitaxy on 2D materials, with an emphasis on the diverse interactions involved, including (i) the intermolecular interactions between the deposited molecules, (ii) the molecule-2D material interactions, and (iii) the molecule-substrate interactions through the 2D material. The interplay between these interactions determines the dimension, interfacial orientation, crystal packing, morphology, and electronic properties of the epitaxial layer. We further review the state-of-art applications, which might benefit from tailoring molecular interactions at 2D materials interfaces.