The present study tests the potentiality of a novel microwave based regenerating permeable reactive barrier (MW-PRB) system as combined treatment for Cs-contaminated groundwater. Granular activated carbon (GAC) was selected as adsorptive materials in batch and column MW-regeneration experiments. Experimental and modeling data were elaborated for technical and economic considerations in order to assess the MW-PRB feasibility jointly with essential information regarding its real field applicability. Batch experiments investigated the effects of 10 adsorption-MW regeneration cycles under different MW irradiation conditions (applied electric field = 200–460 V m⁻¹; irradiation times = 1–15 min) by assessing GAC variation properties in term of regeneration yield (δ), specific area and weight loss (WL) variation. Column tests were carried using a dedicated setup essentially including a column filled with GAC implanted in a MW oven cavity (MW electric field of 385 V m⁻¹, irradiation times 5–15 min). Lab-scale results shown the ability of MW in Cs removal from GAC as demonstrated by regeneration yield (δ = 79–110%) and WL (6.78% for 10 cycles) values. This was confirmed in dynamic conditions by data from MW-column tests highlighting the highest Cs removal of ~80% when the maximum regeneration time was applied. Residual Cs concentration in breakthrough curves fitted well with the proposed Yoon and Nelson model (R² = ~0.97). Results from techno-economic analysis revealed the MW-PRB viability and its advantages also in comparison with conventional PRB systems, demonstrating the concept of combined MW-PRB treatment. Saved cost obtained demonstrated in fact the potential cost effectiveness of MW-PRB system and, consequently, the implementation of novel approach is encouraged. Calculated PRB longevity vs groundwater velocity curves are useful in order to predict long-term PRB performance and the response of the remediation activities, as well as for guiding the design and the scaling-up of MW-PRB treatment.