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This paper develops an integrated framework to examine the determinants of industry-science cooperation in the general process of developing innovation. Based on the literature review and using firm-level data on innovation strategies of 805 manufacturing enterprises in Russia we investigate what are the incentives to firms (1) to cooperate with universities and R&D organizations and (2) to choose a particular mode of interaction that ranges from purchasing S&T services to a full scale original R&D aimed at creating new-to-market innovation. We suggest that a broad range of intramural and external determinants, including competition regime, absorptive capacity, technological opportunities, appropriability conditions, public support, as well as barriers to the practical application of R&D results influence the firm’s decision on cooperation with knowledge producers. The findings indicate that the scale of industry-science linkages in Russian manufacturing is limited and generally hampered by low propensity of business to the R&D-based innovation strategies.