Industry 5.0, as proposed by the European Commission, marks a paradigm shift from profit-oriented production towards a model that prioritizes human well-being and environmental sustainability. In contrast to Industry 4.0, which emphasized automation and efficiency, Industry 5.0 integrates advanced technologies with a human-centric and eco-conscious approach. The agrifood sector—particularly the winemaking industry—is a strategic application area, given its socio-economic relevance and environmental impact, especially in countries such as Italy. In response, we developed CANTINA 5.0, a research initiative aimed to operationalize Industry 5.0 principles in Italian wineries through a multidimensional approach centered on sustainability, human factors, and product quality. The research structure is based on four interconnected pillars: (i) quality of life monitoring via wearable sensors and structured questionnaires assessing workers’ physical and psychological conditions; (ii) environmental monitoring of pollutants within wine cellars using both IoT-based devices and conventional GC-MS analysis; (iii) sustainability assessment through standardized questionnaires addressing environmental practices and social responsibility indicators, with a focus on workforce well-being; and (iv) wine quality evaluation, combining chemical profiling, expert sensory panels, and emotional response tracking of consumers using wearable devices. To date, 20 wineries (12 in Friuli-Venezia Giulia, 8 in Tuscany) have participated. All completed sustainability and well-being surveys; selected facilities underwent environmental monitoring, and workers in some wineries wore smartwatches during harvest and non-harvest periods. Wine samples were analyzed chemically and sensorially, while emotional responses to wine tasting—alone and paired with music—were collected during five public events. Preliminary results show high stakeholder engagement and public interest. Future work will extend data collection and develop targeted dissemination strategies to foster the adoption of Industry 5.0 in national and European R&D frameworks.