Life-science clusters have been extensively researched; however, comprehensive models in terms of resources and capabilities appear to be rare. Such models are needed to assist the analysis of sources of success of some clusters, to distinguish successful from less successful or mature from early stage locations, and to help formulate templates for developing emerging and peripheral locations. Due to the scarcity of systemic and holistic models, a model is proposed and is empirically tested during a decade-long research programme combining separate qualitative and quantitative studies analysing four clusters: Central Scotland, Oxford, South West England and Ireland. Through successive stages of testing, the model is shown to be a reliable tool capable of assessing cluster traits and performance in terms of resources and capabilities, by uncovering systematic differences across the studied locations. The model application generates surprising findings which could not have been reached through simpler measures and which would be difficult to identify or theorize without the model. Confirmed are consistent associations across cluster resources and capabilities, outcomes, and institutional conditions. The model helps distinguish globally leading, mature clusters from peripheral, less-mature locations and assists the theorization of locations across life-cycle stages.