Short-term medical missions (STMM) have become increasingly popular among healthcare professionals of all disciplines and experience levels. It is estimated that volunteer teams travelling from the U.S. to low and middle-income countries (LMICs) spend upwards of $3.7 billion in annual expenses (Caldron, 2016). While these missions can provide significant benefits to patients and invaluable experiences to practitioners, the relatively uncoordinated and unregulated nature of such practices has raised questions about their overall effectiveness, longer-term impact, and potential consequences. The Partnership for Quality Medical Donations (PQMD) launched the Healthcare System Strengthening/Medical Missions Initiative (HSSMM), a 3 -year project, which aims to improve the practice of STMMs to better support and strengthen local healthcare systems. With well-researched and an improved framework for best practice medical missions can better help address longer-term needs and contribute to improved health outcomes in host communities, in LMICs. High quality, inclusive and reciprocal partnerships with local healthcare providers and ministry of health officials are critical for open dialogue, trust and improved coordination.Developing an in-country framework required the involvement of many different stakeholder participants including: the Ministry of Health; local and International Health Care Providers; Professional Associations; International and National Non- Governmental Organizations (NGOs); Medical and Nursing Schools; and Community leaders. To date, assessments have been conducted in Honduras, Malawi and the Philippines. Full REB approval (file #25339) from Trent University, Peterborough, ON, along with organizational letters of support from PQMD and Americares. There was an overall acceptance and positive response to the best practice guidelines. Naturally, licensing and country based tools will be required for implementation. Examples of benefits, challenges and lessons learned will be shared. Guideline development for Medical Missions representative of both sending and host organizations from Honduras, Malawi and Philippines are now available. Enhanced awareness by professional affiliations, colleges and universities from High Income Countries (HIC), thought leadership forums and networking are key to future change activities. There is a need for a more robustly developed community of practice (COP) platform for the sharing of documents, knowledge and promoting dialogue between sending and host STMM communities. A newly developed COP infrastructure will include both domestic and international mission stakeholders.