The integration of two-dimensional (2D) materials with molecular chemistry to create molecule-2D material heterostructures presents a compelling strategy for advancing material design and applications. This approach provides precise control over the structure and properties of 2D materials, effectively addressing challenges in their production and fabrication. Among these, molecule-transition metal dichalcogenide (mTMD) heterostructures have garnered significant attention due to their distinctive electronic, optical, and catalytic properties, as well as the intriguing emergent states and phenomena resulting from interactions with adjacent molecular and material layers. Achieving the desired electronic and optical properties in these heterostructures hinges on carefully controlling the interactions at the molecule/TMD interfaces. This minireview highlights recent progress in mTMD heterostructures, emphasizing the principles underlying interface interactions, molecular arrangement, and innovative synthetic methodologies.