A design of an advanced sensing material, such as MoS2, is imperative to enhance the sensing performance of a sensor. Because their usage alone for developing a practical sensor is impeditive owing to low gas response and slow response/recovery kinetics. Here, we report a high-performance NO2 gas sensor using a hybrid of temperature-assisted sulfur vacancy within the edge-oriented vertically aligned MoS2 (Sv-MoS2) and crumpled reduced graphene oxide (rGO) particles. Interestingly, the Sv-MoS2 functionalized by optimized rGO concentration exhibited a significant enhancement of response to NO2 (approximately three times higher than that of pristine vertically aligned MoS2) with fast response (< 1 min) and complete recovery. Such a large improvement in the sensing performance could be attributed to controlled electrical/chemical sensitization level of MoS2 through controllable vacancy and interface engineering. The vacancy engineering offers abundant active sites through creating sulfur vacancy in additionally rich edge active sites of vertically oriented MoS2 for more electronic interaction with gas molecules. While interfacing of p-type rGO particles with n-type MoS2 leads to multiple out-of-plane vertical nano-heterojunctions as a sensitizing configuration for boosting the performance of the sensor. This paper opens up a new approach towards improving the sensing activity of a 2D material via a synergistic vacancy and interface engineering. © 2001-2012 IEEE.