University spin-offs (USOs) have attracted significant attention from scholars and policymakers as an important mechanism for science-based innovation. The debate on how USOs generate innovation outcomes has often considered the role of tangible assets, while the important role of intangible assets has been less explored and remains poorly defined. Yet emerging research suggests that it is these intangible assets, especially in the early stages, that have a critical influence on a USO’s survival and future success, highlighting a need for a better understanding of how intangible assets impact science-based innovation. Drawing from several streams of literature, we provide the first conceptual definition of intangible assets in the context of sciencebased innovation through USOs. To clarify the role of intangible assets, we conduct a systematic literature review of the leading innovation management journals and inductively derive a framework outlining the antecedents, processes, and outcomes of science-based innovation through USOs. Our novel framework reveals the relevance of intangible assets on science-based innovation through USOs and identifies potential research directions to improve the understanding of this topic. For example, we find a clear need for studies using more sophisticated measures of USO innovation and a need for more studies that provide an understanding of why USOs fail. We conclude by offering recommendations for practitioners and policymakers to better leverage intangible assets to enhance science-based innovation through USOs.