Today’s workplace is becoming more multinational and culturally diverse than ever, both in terms of U.S. organizational employment and the greater global economy. While interest in cross-cultural training has grown as a result, however, there remains a dearth of scientific theory and empirical investigation supporting it. More specifically, there is scant information on key competencies that are needed for employees to perform global work effectively. This work addresses this gap in knowledge by briefly reviewing the history and current state of cultural competency across disciplines. A systematic and qualitative literature review of 39 studies, each involving empirically-tested cross-cultural interventions, was conducted. We review empirical and field-based research to distill and define cultural competencies that are key for modern organizations, proposing a novel framework that also incorporates corresponding interventional methods. Nine key competencies are identified and categorized into a novel theoretical framework of three domains. We conclude by making practical, scientifically-backed recommendations for scientists and practitioners alike.