Empathy is integral to social relationships; however, frequent exposure to emotionally demanding situations can lead to burnout, particularly in professions such as medicine. This situation can be further exacerbated by global crises, such as the COVID-19 pandemic and wars. Burnout is characterized by emotional exhaustion and depersonalization, with serious consequences, including addiction and even suicide. This chapter investigates relevant psychological and neuroimaging studies to elucidate empathy-induced burnout, considering factors such as cognitive flexibility, alexithymia, and a sense of coherence. To alleviate empathy-induced burnout, it is crucial to maintain a flexible balance between empathic engagement (emotion recognition) and objective clinical distancing. Furthermore, fostering cognitive flexibility and a sense of control/coherence can mitigate maladaptive distress and depersonalization. These results provide insights into neurocognitive dynamics and strategies for preventing burnout in professions facing unprecedented challenges. Understanding these dynamics is vital for promoting mental health and well-being among professionals exposed to emotional distress.