Communities of practice (CoPs) interact with a range of external stakeholders who collectively influence the direction of the community and the achievement of its goals. In the case of multi-actor co-innovation partnerships, which are perceived as a type of combination between a community of practice and innovation network in this paper, internal and external interactions consequently influence the ability of these partnerships to co-innovate. The aim of this contribution is to develop an analytical framework to understand the factors and processes that enable or hinder interactions, both within and external to multi-actor co-innovation partnerships. The analytical framework was built around interactions with funding mechanisms, external stakeholders, the context/environment, and societal challenges, along with interactions within the partnership. Each of these five interactions is influenced by structures and capacity, along with how these combine to overcome the challenges faced by the partnership. For this study, 30 case study multi-actor co-innovation partnerships from across Europe were selected and analysed according to the framework. The results show that interactions with funding bodies can lead to partnerships adapting to what they perceive to be the goals of the funding body, and sometimes to the overpromising of expected outputs in an effort to win scarce funding. The reflection of societal needs in the goals of funding bodies could thereby capitalize on the motivations and aspirations of partnerships to combine socio-economic and environmental benefits at both individual and societal levels. Factors that enable partnerships to achieve their own goals are commonly based around the inclusion or recruitment of experienced partners with existing networks, in which the partnership may be embedded, that can facilitate internal collaboration and navigate the external environments, such as political structures and market conditions.