The risk associated with chemical, biological, radiological, nuclear, and explosive (CBRNe) threats in the last two decades has grown as a result of easier access to hazardous materials and agents, potentially increasing the chance for dangerous events. Consequently, early detection of a threat following a CBRNe event is a mandatory requirement for the safety and security of human operators involved in the management of the emergency. Drones are nowadays one of the most advanced and versatile tools available, and they have proven to be successfully used in many different application fields. The use of drones equipped with inexpensive and selective detectors could be both a solution to improve the early detection of threats and, at the same time, a solution for human operators to prevent dangerous situations. To maximize the drone’s capability of detecting dangerous volatile substances, fluid dynamics numerical simulations may be used to understand the optimal configuration of the detectors positioned on the drone. This study serves as a first step to investigate how the fluid dynamics of the drone propeller flow and the different sensors position on-board could affect the conditioning and acquisition of data. The first consequence of this approach may lead to optimizing the position of the detectors on the drone based not only on the specific technology of the sensor, but also on the type of chemical agent dispersed in the environment, eventually allowing to define a technological solution to enhance the detection process and ensure the safety and security of first responders.