In two-dimensional organic-inorganic heterostructures (2D O-I HS), interlayer coupling has emerged as a new design parameter for engineering their electronic and optoelectronic properties, essential for designing future excitonic and optoelectronic devices1-5. However, the further exploration of interlayer couplings is limited by their weak strength and ineffective tuning strategies6,7, due to the inconsistent material quality and the bulky size of organic counterparts8-10. Here, we integrate 2D pentacene single crystals with monolayer MoS2 to achieve strong interlayer coupling and effective tuning through a twisting method. We confirm this strong coupling through calculated lower interlayer spacing (~2.70 Å), high charge transfer efficiency (~61%)11-13 and a high coupling strength of ~2.72 at a twist angle of ~32°. Both density functional theory (DFT) calculations and experimental results demonstrate the remarkable electrical control over interlayer couplings by adjusting electrical band alignments. This control over interlayer couplings helps to untangle the diffusion of neutral excitons and trions14,15, which have diffusion lengths of ~1.95 μm and 0.93 μm, respectively. Our results underscore the significant tunability of interlayer couplings and relaxations within O-I systems via twist angles, offering new avenues for developing high-performance vertical transistors, logic devices, photodetectors and photovoltaic devices.