HERCCULES aims at defining a first-of-a-kind, integrated and replicable approach for the implementation of the whole CCUS chain to two strategic sectors of the circular economy - Cement and Energy-from-Waste (EfW) – in an area – Italy and Greece – where the industrial promise of CCUS is largely unexplored. Leveraging on the potential of two clusters of emitters in Northern Italy (cement + EfW) and Greece (cement), HERCCULES will pave the way towards the implementation of the first full-scale CCUS chain in Southern Europe. Technological, infrastructural, safety, societal, regulatory and financial issues will be addressed by a multidisciplinary approach to build an “HERCCULES paradigm” comprising nine basic chapters. 1) TRL7-8 demonstration of 2 flexible and retrofittable CO2 capture technologies, to be tested in 2 large-scale cement plants + 1 EfW plant with residual waste/biomass feed to approach nearly zero or negative emissions (>9000 h of tests). 2) Design of the optimal CO2 transport network for utilization and storage under different infrastructural evolution scenarios. 3) TRL8 Geological storage of captured CO2 in the two most advanced CO2 sites in Southern Europe (Prinos and Ravenna). 4) Demonstration in industrial environment of novel CO2 mineralization solutions and re-use technologies for the production of a breakthrough hydraulic binder enabling the industrial production of a carbon-sink concrete (>1000 h of tests). 5) Experimentally-supported, Techno-Economic Analyses with risk assessment to ensure the safety of the full CCUS chain. 6) Advancement of societal readiness through a participative approach. 7) Identification of business models and financial mechanisms tailored to CCUS. 8) TRL8-9 pre-FEED studies on the most promising HERCCULES implementation options. 9) Ad-hoc case studies to verify the replicability of the HERCCULES paradigm. Know-how, data and models will converge into a dedicated exploitation plan to seed CCUS across Europe.