Two-dimensional van der Waals heterostructures (2D-vdWHs) stacked from atomically thick 2D materials are predicted to be a diverse class of electronic materials with unique electronic properties. These properties can be further tuned by sandwiching monolayers of planar organic molecules between 2D materials to form molecular 2D-vdW heterojunctions (M-2D-vdWHs), in which electricity flows in a cross-plane way from one 2D layer to the other via a single molecular layer. Using a newly developed cross-plane break junction (XPBJ) technique, combined with density functional theory calculations, we show that M-2D-vdWHs can be created, and that cross-plane charge transport can be tuned by incorporating guest molecules. More importantly, the M-2D-vdWHs exhibit distinct cross-plane charge transport signatures, which differ from those of molecules undergoing in-plane charge transport.