The catalytic modifications of gas sensors have been typically classified according to spill-over  and  and electronic sensitization mechanisms, and are related to the presence of noble metals nanoparticles dispersed in the sensing material. The addition of other metal cations into the crystal structure  has also been extensively investigated, with several studies encompassing a huge range of materials compositions. The field of catalysis anyway contains a huge catalog of materials architectures that could still be exploited for improving the response of chemoresistive sensors. The TiO2–V2O5 system  and  is of particular interest for the following reasons: (1) it is a well-known catalyst for the Cathepsin G Inhibitor of organic compounds  and , which is at the basis of the sensing mechanisms of many organic vapors; (2) it could be the prototype of a novel category of materials for gas sensors, where a more active surface layer boosts the response of a usually less active core material. Some studies inspired by this system have been published , , , , ,  and , but in our work we present a fully colloidal version of the system, going beyond the classical impregnation and/or doping concepts. In particular, in this paper we present the sensing behavior of TiO2–V2O5 nanocrystals toward two organic analytes like ethanol and acetone. We begin by showing that surface addition of V2O5 remarkably improves the sensor response with respect to pure TiO2. Then, we present a systematic exploration of the sensing trends specifically aimed to show that the effect of the V2O5 layer addition can be interpreted as a catalytic effect, in terms of lowered best operating temperature and simultaneously enhanced response. The results open the way for the design of whole class of novel sensing architectures.