Systematic innovation methodologies—such as TRIZ, Design Thinking, and Lean—are being hybridized, challenged, and redefined through integration with artificial intelligence. In this Special Issue, we adopt a broad interpretation of systematic innovation, encompassing not only traditional industrial engineering approaches but also organizational, technological, product/service, and financial innovations. Moving beyond the narrative of simple technology transfer, we explore how diverse cultural contexts, rapid digitalization, and pressing societal challenges are reshaping the very practice of systematic innovation in tandem with AI capabilities. We invite interdisciplinary contributions that examine the tension between structured methodologies and the fluidity of modern business ecosystems, particularly as AI becomes a core enabler and disruptor of innovation processes across multiple domains—from business models and corporate structures to market-creating products and novel financing mechanisms. From AI-driven product development and leaninfused supply chains to frugal innovation and service design, this issue seeks empirical and theoretical updates on how systematic innovation is being localized, digitized, and augmented by AI to address complex challenges such as sustainability, aging populations, and urbanization. By bridging engineering, design, organizational behavior, public policy, finance, and data science, this Special Issue aims to capture how regions worldwide are not merely adopting systematic innovation but fundamentally transforming it through AI integration for a new era.