Visual inspection of luggage using X-ray technology at airports is a time-sensitive task that is often supported by automated systems to increase performance and reduce workload. The present study evaluated how time pressure and automation support influence visual search behavior and performance in a simulated luggage screening task. Moreover, we also investigated how target expectancy (i.e., targets appearing in a target-often location or not) influenced performance and visual search behavior. We used a paradigm where participants used the mouse to uncover a portion of the screen which allowed us to track how much of the stimulus participants uncovered prior to their decision. Participants were randomly assigned to either a high (5-s time per trial) or a low (10-s time per trial) time-pressure condition. In half of the trials, participants were supported by an automated diagnostic aid (85% reliability) in deciding whether a threat item was present. Moreover, within each half, in target-present trials, targets appeared in a predictable location (i.e., 70% of targets appeared in the same quadrant of the image) to investigate effects of target expectancy. The results revealed better detection performance with low time pressure and faster response times with high time pressure. There was an overall negative effect of automation support because the automation was only moderately reliable. Participants also uncovered a smaller amount of the stimulus under high time pressure in target-absent trials. Target expectancy of target location improved accuracy, speed, and the amount of uncovered space needed for the search. Significance Statement: Luggage screening is a safety-critical real-world visual search task which often has to be done under time pressure. The present research found that time pressure compromises performance and increases the risk to miss critical items even with automation support. Moreover, even highly reliable automated support may not improve performance if it does not exceed the manual capabilities of the human screener. Lastly, the present research also showed that heuristic search strategies (e.g., areas where targets appear more often) seem to guide attention also in luggage screening.