The ability to react to unexpected auditory stimuli is critical in complex settings such as aircraft cockpits or air traffic control towers, characterized by high mental load and highly complex auditory environments (i.e., many different auditory alerts). Evidence shows that both factors can negatively impact auditory attention and prevent appropriate reactions. In the present study, 60 participants performed a simulated aviation task varying in terms of mental load (no, low, high) concurrently to a tone detection paradigm in which the complexity of the auditory environment (i.e., auditory load) was manipulated (1, 2 or 3 different tones). We measured both detection performance (miss, false alarm, d’) and brain activity (event-related potentials) associated with the target tone. Our results showed that both mental and auditory loads affected target tone detection performance. Importantly, their combined effects had a large 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 and auditory loads and miss rates were associated with disrupted brain responses to the target tone, as shown by a reduced P3b amplitude. In sum, our results highlight the importance of balancing mental and auditory loads to maintain efficient reactions to alarms in complex working environment.