Physician associates/assistants (PAs) and their equivalents offer a solution to the supply and demand crisis to alleviate global healthcare needs. This study investigated how PA and PA equivalents address global healthcare needs across different healthcare systems, revealing recommendations for their use. The study also sought to catalog the global healthcare needs that PAs and equivalents are successfully alleviating, the roles in which they function, and the barriers facing implementation. A systematic review was conducted from October 2021 to April 2022 and rerun in June 2023 following PRISMA 2020 guidelines; additionally, supporting interviews were conducted with PAs and global health experts. Primary outcomes were geographic region, economy, healthcare needs, and healthcare systems. Secondary outcomes were PA use, license recognition, and successes or barriers when implementing PAs. The literature and interviews focused on the global use of PAs and PA equivalents in six geographic regions, 63 countries, and five US territories where PAs or PA equivalents are employed, have been employed, are volunteering, or are being considered to support global healthcare needs. Most countries have a developing economy and an out-of-pocket healthcare system. PAs and PA equivalents hold 35 different practice titles, and most work in primary care. PAs alleviate healthcare shortages and economic disparities, specifically related to inequitable healthcare access. Globally, the profession is limited by a lack of legislation, regulation, and support. PAs and PA equivalents worldwide belong to an adaptable profession that has well-documented success in alleviating the global healthcare shortage and addressing healthcare needs. Countries desiring PAs or PA equivalents should identify their specific needs, train their existing workforce, employ pilot programs, and focus on seeking early legislation and regulation. Broad support for existing PA and PA equivalent international organizations is recommended for global collaboration. This study serves as a guide for those advocating for the continued or future implementation of PAs and PA equivalents in their own country and provides a comprehensive resource to aid in the globalization of this profession. We offer recommendations to address the dire healthcare needs and workforce shortage faced across the globe.