Job satisfaction has been frequently studied in different types of work settings including higher education; however, there are limited studies that focus on foreign-born faculty members in the U.S. Also, studies that focus on using self-esteem and mentoring to predict faculty job satisfaction are limited. The purpose of this quantitative study was to compare U.S.-born and foreign-born faculty members’ job satisfaction in 21 research universities based on their country of origin, marital status, faculty ranking, tenure, and mentoring status. Moreover, the study sought to explore the relationship among mentoring, self-esteem, and job satisfaction of U.S.-born and foreign-born faculty members. The instruments used in the study were the Job Satisfaction Scale, Mentorship Effectiveness Scale, and Rosenberg Self-Esteem Scale. The results showed that there was no significant difference in U.S.-born and foreign-born faculty members’ job satisfaction. In addition, there was no significant difference in U.S.-born and foreign-born faculty members’ job satisfaction based on marital status, faculty ranking, and tenure status. However, the results showed that job satisfaction of U.S.-born and foreign-born faculty members who were mentored was significantly different than those who were not mentored. The correlation between self-esteem and faculty job satisfaction was positively correlated, indicating one unit increase in self-esteem would lead to one unit increase in job satisfaction. Furthermore, multiple regression analysis revealed that mentoring and self-esteem as a set was a significant predictor for faculty job satisfaction, accounting for 15.4% of the variance in U.S.-born and foreign-born faculty job satisfaction. The results of this study can be a valuable resource to institutions and institutional administrators in recruiting and hiring quality U.S.-born and foreign-born faculty members as well as developing mentoring programs that may help to ease their career transition and improve their job satisfaction.