This article focuses on a major human factors–related issue that includes the undeniable role of cultural factors and cockpit automation and their serious impact on flight crew performance, communication, and aviation safety. The report concentrates on the flight crew performance of the Boeing 777–Asiana Airlines Flight 214 accident, by exploring issues concerning mode confusion and autothrottle systems. It also further reviews the vital role of cultural factors in aviation safety and provides a brief overview of past, related accidents. Automation progressions have been created in an attempt to design an error-free flight deck. However, to do that, the pilot must still thoroughly understand every component of the flight deck – most importantly, the automation. Otherwise, if pilots are not completely competent in terms of their automation, the slightest errors can lead to fatal accidents. As seen in the case of Asiana Flight 214, even though engineering designs and pilot training have greatly evolved over the years, there are many cultural, design, and communication factors that affect pilot performance. It is concluded that aviation systems designers, in cooperation with pilots and regulatory bodies, should lead the strategic effort of systematically addressing the serious issues of cockpit automation, human factors, and cultural issues, including their interactions, which will certainly lead to better solutions for safer flights.