This seminal study explores systemic sustainability within the Industry 5.0 paradigm, using the strategic lens of geoanthropology to shape the emerging concept of Industry 6.0. A transdisciplinary approach is adopted, integrating geoanthropological insights into the analysis of the Italian ceramic district. Seven key factors are considered: resource consumption, production dynamics, innovation, environmental impact, social impact, market dynamics, and economic impact. Historical events such as changes in Italian industrial policy, market slowdowns, and the COVID-19 pandemic are identified as significant for the sector. A contingent analysis tailored to the unique characteristics of the ceramic district provides an in-depth understanding of its challenges and opportunities. The incorporation of geoanthropology provides a transdisciplinary perspective that allows for an in-depth examination of the complex interactions between people and their environment in an industrial setting. The study highlights the central role of innovation, digitalization, and government policies in driving positive changes in production efficiency, market dynamics, and economic impact. Nevertheless, challenges remain, including the delicate balance between environmental sustainability and resource consumption, as well as the effective management of the social impacts of digitization. To address these challenges, a systemic sustainability index derived from geoanthropological insights is proposed as a pragmatic tool to measure and guide the development of sustainability initiatives in the ceramic district. The results of this study not only pave the way for new horizons in sustainability assessment but also provide valuable insights for industrial district managers to formulate strategies that foster organizational flexibility and resilience.