Why are some universities capable of obtaining better results from the interactions with firms than others? So far, literature in university-industry cooperation (UIC) has answered this question by studying the role of technology transfer offices, incentive and intellectual property protection policies and some organizational features. In this paper we present a systemic framework that explains how universities should organize to outperform their competitors in knowledge exploitation. Our core idea is that the success of universities in collaborative agreements with non-academic organizations, in addition to environmental and individual characteristics, stems from the interaction of four organizational factors, namely, support mechanisms (structures and policies), strategic orientation, management abilities and culture.