We aimed to describe the characteristics of teachers’ engagement and persistence in an innovative multidisciplinary health programme. Participants in this descriptive and comprehensive study consisted of teachers in higher education (veterinary medicine, human medicine, pharmacy, engineers in husbandry) who were involved in the conception and the implementation of an international Master programme called MAN-IMAL. This programme was characterized by interculturality, multidisciplinarity, using technology, active teaching, and learning. We conducted two focus groups, each of which included six participants. A thematic analysis was performed. The constitution of a community of practice through a process of socialization involving teachers, students, and faculty developers around the “One Health” concept had a positive influence on the engagement and the persistence. On the contrary, a lack of leadership sharing in the programme and a lack of recognition by institutional leaders had a negative effect on persistence. Also, the characteristics of the programme had different impacts on stress perceived by the teachers and, therefore, could have both a negative and/or a positive influence on persistence. Our results suggest that the development of a community of practice in an innovative multidisciplinary health programme around a unifying concept like “One Health” can have a positive influence on teachers’ engagement and persistence, even in a challenging context.