•Technological innovations tend to rely primarily on the STI mode.•Non-Technological innovation tend to rely priimarily on the DUI mode.•Context-specificity matters in relation to the effectiveness of local vs. global collaborations. In this paper, we join the debate on business innovation modes that originates from the wider literature on innovation systems. These specific contributions identify and study the impact of different innovation modes, particularly the mode focused on scientific and technologically-based innovation (STI) vs. the mode based on learning-by-doing, by-using, and by-interacting (DUI). Echoing the seminal contribution by Jensen et al. (2007) and a range of other studies, we confirm the importance of the combined STI&DUI interaction mode, which has a stronger impact on innovation output (technological and non-technological) than the two separate individual modes. Additionally, we propose a novel hypothesis on the effectiveness of firm's interaction modes. We argue that the independent STI mode has a stronger effect on technological innovation, whereas the independent DUI mode has a stronger impact on non-technological innovation. In addition, in line with works on the geography of innovation, and innovation systems, we try to determine the impact of regional vs. global DUI and STI interactions on technological and non-technological innovations. In this case, we expect that in diverse geographic locations, businesses tend to adopt their own context-specific interaction modes, which produce a differentiated impact on innovation output. This study is applied to a large sample of firms in the context of the Basque Autonomous Community in Spain.