To contribute to the debate on climate-proof urban regeneration, the illustrated study seeks to understand how the provision of new multiscalar, multidimensional, and integrated planning tools based on sustainable and resilient strategies can guarantee high levels of urban, environmental, and energy efficiency and quality, as well as circularity of resources, counteracting the effects deriving from climate change. Starting from some regulatory and design references that integrate a new ecologically oriented city model into the planning of urban projects, the contribution identifies in the construction of green and blue infrastructures (GI) new design metaphors capable of improving biodiversity; favoring ecological and energy transition; restoring the quality of the air, water, and soil environmental matrices with natural solutions; and making cities truly inclusive, sustainable, and resilient. The methodology adopted for the design of the “Acilia–Madonnetta” Urban and Metropolitan Centrality in the Municipality of Rome simulates a planning process for part of the X Municipality by applying an iterative and interscalar logic, an articulation of levels and phases with the aim of prefiguring the construction of a GI characterized by new ecological-environmental and functional endowments strictly related to the promotion of an efficient, smart, and green city. The contribution highlights the potential and limits of the proposed experimentation, relating both to the quality and innovation of design solutions and possible evolutionary lines and to the lack of clear institutional governance that is limiting the implementation of projects.