Background: The shortage of physicians in Turkey is a highly critical emergency. In fact, physicians’ migration to developing or high-income countries, defined as brain drain, threatens the sustainability of the national healthcare system. Aims: This study explored the driving factors associated with Turkish Physicians’ brain drain, including high-economic inflation, social-politics, poor-living, equity, violence, and the desire to practice medical activity abroad. Methods: A cross-sectional survey of 1,861 Turkish physicians aged 25 to 65 years old was conducted employing the Brain Drain questionnaire, the Depression Anxiety Stress Scale (DASS-21), the Patient Health Questionnaire 9 (PHQ-9), and the Fatigue Assessment Scale (FAS). Results: Significant differences were observed among physicians staying in Turkey versus considering migration to Western countries, regarding their age, gender, marital status, educational level, occupational status, work years, hospital night shifts, income, and cigarette/nargileh smoking habits ( all p ⩽ .018). The main reasons for brain drain included transport problems, harassment, low salary, malpractice, bad environment, job insecurity, workload, burnout, treating difficult patients, inadequate postgraduate systems, peer-pressure, health safety concerns, and favoritism in the workplace, as well as stress and depression caused by work overload. In fact, depression, anxiety, stress, fatigue, and burnout varied significantly among the different groups of physicians (all p ⩽ .013). Additionally, key predictors of brain drain were better job opportunities, poor hospital management (in Turkey), job-related stress, dealing with difficult patients, research deficiencies, workload, burnout, transportation issues, short consultation time, low salary, and fatigue. Among the general factors contributing to the brain drain in the Turkish Health System, we identified significant issues related to research deficiencies, compulsory working duties, poor quality of postgraduate, inadequate medical-schools, poor hospital management, and shortage of consultants. Conclusion: Physicians’ migration is a major global public health concern, leading to substantial risks for healthcare services, especially in Turkey. Many physicians decide to migrate to work in Western countries.