Organic–inorganic 2D heterostructures combine the high optical absorption of organic molecules with exciton-dominated optical properties in layered transition metal dichalcogenides (TMDs) such as MoS₂. Critical to the interaction and the optical response in such hybrid systems is the electronic band alignment at the interface between the two species. Here, the coupling of monolayers of perylene derivatives is investigated with bilayer MoS₂. In particular, variation in the perylene orientation on the MoS₂ surface is identified using Raman spectroscopy and scanning probe microscopy. Low-temperature optical spectroscopy reveals orientation-dependent interlayer exciton formation. Furthermore, power-dependent photoluminescence measurements provide insight into the modified interlayer charge transfer in these heterostructures. A saturation of interlayer states is found under high excitation power when the perylene molecules are in a perpendicular orientation to the surface that leads to electron accumulation in the MoS₂, whereas parallel alignment of the perylene molecules leads to enhanced populations of organic–inorganic interlayer excitons. This work provides insights into the optimization of organic–inorganic heterostructures, with particular relevance to applications for optoelectronic and excitonic devices.