As for the recent scientific findings, carbon neutrality is no more sufficient within the research for a sustainable development, as climate change effects are becoming crucial factors to be considered. Therefore, in developing strategies and applying design technologies for sustainability in urban settlements, a focus on climate neutrality is required, to build climate resilience together with energy efficiency. This paper presents an experimental methodology applied within the ABITAlab activities for the assessment of the Urban Regeneration Integrated Plan (PIRU) for the Mediterranean city of Taranto. In this experience the Advanced Sustainable Design (ASD) was applied by addressing both energy efficiency and climate resilience for climate neutrality. The importance of the experimentation is defined by the relation upon which, since Regenerative Design principles apply to ASD, the presented assessment methodology is applied to the ASD Process, through which, by studying regenerative scenarios, the goal of production of positive environmental and social impacts overcome the concern for the reduction of negative environmental impacts. The paper is structured as follows: after research reported in the literature section, the proposed assessment methodology is built interpolating three types of validated assessment methodologies to address climate neutrality: (1 and 2) through NbS and SUDS for climate resilience; (3) through PEDs for energy efficiency. Then, the methodology is validated through its application to the presented project experience within a regenerative scenario of transformative resilience. At the end, the experimentation results validate: (a) the workflow methodology divided in three different steps; (b) the scientific contribution of the methodology based on the integration of three different assessment methods. The work presented is validated for the Advanced Sustainable Design for climate neutrality within regenerative scenario, replicable in the Mediterranean area.