Teachers in urban schools experience stress and burnout at levels that significantly impact their mental health and occupational functioning, and contribute to alarming rates of attrition. The current mixed-methods study employed a sample of 162 predominantly White and female urban teachers in the United States to examine the role of personal and contextual factors, and responses to situational challenges, in predicting burnout. Results revealed that multiple personal factors and responses to situational challenges predicted burnout. Notably, higher levels of professional and social-emotional support predicted lower levels of burnout across multiple dimensions, while internal locus of control and digestive responses to situational challenges, respectively, predicted higher levels of Personal Accomplishment and Emotional Exhaustion. Implications include further avenues of research and suggestions for supports which function as teacher resources in the mitigation of burnout and promotion of wellbeing for urban teachers.