An accurate assessment of mental workload and expertise level would help improve operational safety and efficacy of human computer interaction for aerospace applications. The current study utilized functional near-infrared spectroscopy (fNIR) to investigate the relationship of the hemodynamic response in the anterior prefrontal cortex to changes in mental workload, level of expertise, and task performance during learning of simulated unmanned aerial vehicle (UAV) piloting tasks. Results indicated that fNIR measures are correlated to task performance and subjective self-reported measures; and contained additional information that allowed categorizing learning phases. Level of expertise does appear to influence the hemodynamic response in the dorsolateral/ventrolateral prefrontal cortices. Since fNIR allows development of portable and wearable instruments, it has the potential to be deployed in future learning environments to personalize the training regimen and/or assess the effort of human operators in critical multitasking settings.