The health profile of foreigners in Italy is affected by multiple factors and events, including environmental, microbiological, cultural, and behavioral. To explore nurses’ basic cross-cultural knowledge, and their perceptions of problems that arise in encounters with clients from outside the country, and to suggest solution strategies, we enrolled 327 nurses in an observational, cross-sectional, multicenter study. The findings suggested a need to improve sociocultural skills related to working in a multiethnic society, as early as the first level courses and possibly continue with appropriate master’s degrees and research projects.