Objective: Researchers have begun to examine factors that contribute to professional quality of life (ProQol) and well-being among professionals who provide services to refugees. These professionals are at increased risk of burnout and secondary traumatic stress due to the demands of their work and exposure to clients who have significant trauma histories. This study seeks to examine factors such as mindful self-care (MSC), coping, and meaning in life and how they may impact ProQol and well-being. Method: One hundred and fortyeight multidisciplinary professionals and volunteers in the United States completed an online questionnaire comprising The Mindful Self-Care Scale-33, The Professional Quality of Life Scale, The World Health Organization-Five Well-Being Index, The Brief COPE, and The Meaning in Life Questionnaire. Structural equation modeling was used to examine the relationships between all variables. Results: MSC behaviors had a direct effect on ProQol (β = 0.69, p , .001) and well-being (β = 1.07, p , .001). One's perceived meaning in life had a direct effect on ProQol (β = 0.22, p , .001) and on well-being (β = 0.17, p , .05). Coping experience had a direct effect on well-being (β = 0.71, p , .001) and well-being had a direct effect on ProQol (β = 0.33, p , .001). Conclusion: Based on the findings, future programs directed at supporting these individuals can encourage MSC practices, adaptive coping, and explore aspects of one's job that bring meaning to their life to better support individuals who work with refugees. Clinical Impact StatementResearch examining the professional quality of life and well-being of individuals who work with refugees is early in development but has demonstrated that these individuals are at risk of experiencing burnout due to working with communities with significant trauma histories. The present study examined how one's experiences with coping, meaning, and mindful self-care may relate to one's professional quality of life and well-being. Results indicated that these factors had direct effects on professional quality of life and well-being. These findings can be used to inform future initiatives aimed at supporting these individuals, thus enhancing the quality of care for these communities.