The realization path and mode selection issues for the duality innovation of the scientific small and medium enterprises (SMEs) haven’t obtained a good settlement in China. With the questionnaire investigation and layered regression analysis for 292 scientific SMEs, this paper carried out researches on the realization path and mode selection for the duality innovation for scientific SMEs. The results show that relying purely on the interior path and correspondent paths to realize the duality innovation has no significant lifting functions for the enterprises’ performance, relying purely on the exterior paths and correspondent modes to realize the duality innovation will pose harms to the enterprises’ performance, and by taking the interactive paths between the interior path and exterior path to realize the duality innovation has significant lifting functions for the enterprises’ performance. The duality innovation mode with the interior development innovation and the exterior exploration innovation under this path is lifting the enterprises’ performance to the greatest extent.