Synthetic biology offers many solutions in healthcare, production, sensing and agriculture. However, the ability to rationally engineer synthetic biosystems with predictable and robust functionality remains a challenge. A major reason is the complex interplay between the synthetic genetic construct, its host, and the environment. Each of these contexts contains a number of input factors which together can create unpredictable behaviours in the engineered biosystem. It has become apparent that for the accurate assessment of these contextual effects a more holistic approach to design and characterisation is required. In this perspective article, we present the context matrix, a conceptual framework to categorise and explore these contexts and their net effect on the designed synthetic biosystem. We propose the use and community-development of the context matrix as an aid for experimental design that simplifies navigation through the complex design space in synthetic biology.