This study aimed to evaluate the factors related to the mental health of foreign care workers in Japan’s long-term care (LTC) facilities and compare their results with those of native care workers. We conducted a cross-sectional survey covering 80 LTC facilities across Japan between August and November 2021. The survey mainly included mental health, workload, reward, sense of coherence, loneliness, COVID-19-specific factors and sociodemographic variables. The results show that workload was a distinct feature associated with the mental health of foreign care workers (n = 172) when compared with those of native care workers (n = 154). In addition, we found that the relationship between cultural adaptation and mental health in a sample of foreign care workers was mediated by loneliness and sense of coherence (SOC). Finally, we found that reward, loneliness, SOC, and COVID-19-specific factors had significant impacts on the mental health of both foreign and native care workers. These findings highlight the importance of support measures from the workplace for foreign care workers. Workplace interventions that focus on workload, reward, and sense of coherence strategies are required to address mental health improvement and may still be of value in dealing with the continuing COVID-19 pandemic.