The transition to “Industry 4.0″ and the adoption of Smart Technologies (STs) are generally driven by expectations of gains in productivity, better control over operations and supply chain processes and, therefore, improved competitiveness. These factors are important to achieve success, but sustainable competitive advantage depends on a company's ability to exploit its current assets, while simultaneously exploring new ways of producing value. The ambidextrous balancing of these two areas requires concerted effort and the capacity to balance paradoxical tensions. Literature has thoroughly covered the aspect of how to overcome the trade-off between exploitation and exploration. However, research has only recently started focusing on the pivotal role that digital technologies may play in this process. Our paper contributes to this nascent literature stream by investigating how STs can operate as antecedents of structural ambidexterity. This study relies on the 3rd CINet Survey (2016–2017) involving over 370 companies worldwide. Leveraging on STs and structural ambidexterity as mediators, we used Structural Equation Modelling to show that manufacturing firms with good business performance are in a favorable position to achieve better innovation performances. Our results shed new light on the current debate around the Industry 4.0 transition, with implications for both academics and practitioners.