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Innovation-oriented cross-border collaborations are a means through which developing countries can upgrade technologically. However, the benefits accruing from cross-border collaborations can be asymmetric: while they may possess crucial resources, the developing country may gain little from the collaboration. We examine the context of bioprospecting, defined as the search for biodiversity aimed at commercial exploitation of its biochemical or genetic elements. The well-documented exploitation of developing countries’ natural resources by international partners has made bioprospecting a ‘dark spot’in the cross-border collaboration space. We adopt an abductive configurational approach to investigate the sets of conditions that allow cross-border agreements to include knowledge transfer and innovation, through crisp-set qualitative comparative analysis. Based on our empirical analysis of 59 cases, we provide some policy recommendations about the need for international collaborations and investments to include greater respect for local communities’ fundamental rights and ecosystems.