This work aims to provide an effective structural solution, minimizing the discomfort during the works’ execution, for how to retrofit the Day-Hospital building of the National Cancer Institute “G. Pascale Foundation” in Naples. The structural vulnerability has been preliminarily evaluated for this scope, using linear static and dynamic analyses according to code provisions. The performance index in terms of peak ground acceleration (PGA), both for the life safety (SLV) limit state and the operational (SLO) limit state, has been evaluated. A seismic assessment has been performed by finite element (FE) analyses using the SAP2000 computer program, post-processor VIS15 and plugin SPF. Two main solutions have been proposed to improve the structural performance of the existing building. The first one is based on increasing the thickness of the existing reinforced concrete (RC) cores. The second solution is characterized by strengthening the RC cores using steel plates, steel strips and angles. A comparison of the proposed interventions is provided herein from the technological and financial standpoints.