Modern healthcare is confronted with increasing costs and complexity, progressive population ageing and pandemics triggered by new disease strains and population displacements fuelled by conflicts and climate change. In this context, effective cooperation and interoperability of the participants and their information systems in the healthcare effort becomes paramount. This brings about significant challenges, as healthcare institutions are typically hierarchical and heterogeneous owing to a complex administrative, geographical and historical context. At the same time, governments find it increasingly difficult to rely on ‘silo’ type information and organisational paradigms in order to manage population wellbeing. Thus, there is an increasing need for innovative, holistic and integrated models that take into account all essential aspects, elements and especially life cycles of all the healthcare effort participants. Building on previous research and applications, this paper proposes that the required modelling artefacts can be built using a life cycle-based holistic paradigm enabled by advances in Information Systems, Interoperability, Collaborative Networks and Enterprise Architecture. This multi-faceted approach holds the promise to a sound platform for sustainable solutions to both long and short-term challenges to population health and well-being.