The atomic thickness and flatness allow properties of 2D semiconductors to be modulated with influence from the substrate. Reversible modulation of these properties requires an “active,” reconfigurable substrate, i.e., a substrate with switchable functionalities that interacts strongly with the 2D overlayer. In this work, the photoluminescence (PL) of monolayer molybdenum disulfide (MoS 2 ) is modulated by interfacing it with a phase transition material, vanadium dioxide (VO 2 ). The MoS 2 PL intensity is enhanced by a factor of up to three when the underlying VO 2 undergoes the thermally driven phase transition from the insulating to metallic phase. A nonvolatile, reversible way to rewrite the PL pattern is also demonstrated. The enhancement effect is attributed to constructive optical interference when the VO 2 turns metallic. This modulation method requires no chemical or mechanical processes, potentially finding applications in new switches and sensors.