Expatriate health care and humanitarian aid professionals (N = 159) who were currently deployed internationally participated in this study. We used organizational support theory to guide our examination of the associations between sociocultural adaptation difficulty, perceived organizational support (from organizational headquarters [home] and its foreign subsidiary [host]), and expatriates’ psychological well-being while deployed. Snowball and social networking techniques were used to recruit globally dispersed participants. Participants were mostly female (59%), represented 26 nationalities, and nearly all (99%) were actively working within 53 international settings. Multiple regression analyses indicated that sociocultural adaptation and perceived organizational support from the host and home organizations made significant contributions to expatriates’ psychological well-being. Perceived organizational support from host organization was most strongly associated with expatriates’ psychological well-being while deployed (R2 = .28, p = .000; β [host] = .39, p = .000; β [home] = .12, p = .10). We suggest that host and home organizations employing expatriates work collaboratively to monitor their expatriates’ psychological well-being, perception of the adequacy of support provided, and communicate to provide integrated resources in response to expatriates’ dynamic needs.