This paper examines pilots' responses during a human-in-the-loop simulation to off-nominal conditions.During the simulation pilots used advanced flight deck tools to achieve automated spacing and merging assignments while in cruise, and prior to performing a continuous descent approach (CDA) into Louisville International Airport. The off-nominal conditions were represented by sparse and dense weather-patterned perturbations. Simulation results showed that, for the baseline nominal condition, the pilot response and the operation worked as expected. However, during off nominal conditions, qualitative analysis of traffic scenarios and quantitative data showed that pilot behavior in deviating for weather was difficult to predict, and that pilots often took aircraft-centric strategies to make decisions. These strategies lacked a system-centric perspective that could have allowed them to explore the availability of less disruptive and safer options. These responses formed emergent behaviors that may not have been anticipated by the system, and, can be attributed to the mismatches between the pilot strategies, the intended system/operation functionality, and the procedures/environment. Collectively these mismatches created dispersion in the temporal spacing at the merge point prior to the descent, flight path stretches that are likely larger than required, higher workload, and ultimately unfavorable initial conditions for the CDA operation subsequent to the weather encounter. To further develop the interval managed CDA concept, a number of recommendations were provided for aligning these mismatches by considering the nature of the decision processes within the operational concept and incorporating them into automation designs, by developing a battery of off-nominal scenarios and by conducting simulations to model and specify what the system should and should not do.