Of evolutionary importance, the ability to react to unexpected auditory stimuli remains critical today, especially in settings such as aircraft cockpits or air traffic control towers, characterized by high mental and auditory loads. Evidences show that both factors can negatively impact auditory attention and prevent appropriate reactions in hazardous situations. In the present study, sixty participants performed a simulated aviation task, varying in terms of mental load (no, low, high mental load), that was embedded with a concurrent tone detection paradigm, in which auditory load was manipulated by the number of different tones (1, 2 or 3). We measured both detection performance (miss, false alarm) and brain activity (event-related potentials) related to the target tone. Our results showed that both mental and auditory loads affected tone detection performance. Importantly, their combined effects had a massive impact on the percentage of missed target tones. While, in the no mental load condition, miss rate was very low with 1 (0.53%) and 2 tones (1.11%), it increased drastically with 3 tones (24.44%), and this effect was accentuated as mental load increased, yielding to the higher miss rate in the 3-tone paradigm under high mental load conditions (68.64%). Increased mental load, auditory load, and miss rate, were all associated with disrupted brain response to the target tone as showed by reductions of the P3b amplitude. In sum, our results highlight the importance of balancing mental and auditory loads to maintain or improve efficient reactions to alarms in complex environment.