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This paper presents an overview of a research line developed at the Istituto Centrale per il Restauro within the CHANGES (Cultural Heritage Active Innovation for Next-Gen Sustainable Society) project, funded under the Italian National Recovery and Resilience Plan. The research was developed in different phases: a first one dedicated to the study of the deep background and the state of the art in the ICR background: history, methodologies and research in the field; a second phase was dedicated to the selection of a specific urban art mural, as a key study with conservation problems connected to some of the principal preservation treatments related to the outdoor context; the mural was also identified as a beloved icon in the public space with a profound socio-cultural meaning for the community. Nido di Vespe, created in 2014 by the artist Lucamaleonte is part of a broader artistic project called M.U.Ro-Museum of Urban Art of Rome, an open-air public art museum located in the Quadraro district in Rome, designed by the artist Diavù. A third phase focused on the research in ICR laboratories, specifically addressing: cleaning, reintegration, and protection strategies adapted to dynamic outdoor environments. A multi-step cleaning system based on polyvinyl alcohol-borax semi-interpenetrated hydrogels loaded with nanostructured fluids was developed to selectively remove spray-paint vandalism while preserving the chemically similar original pictorial layers. The reintegration phase investigated acrylic and urea-aldehyde resins as binders to produce compatible, reversible, and UV-traceable retouching and infilling materials. For surface protection, multilayer coating systems incorporating nanoparticles with antimicrobial, photocatalytic, and UV-stabilizing properties were formulated to enhance durability and chromatic stability. Laboratory tests on mock-ups simulating typical street and urban art materials and morphologies showed satisfactory results, while diagnostic investigations on Nido di Vespe provided the reference data to calibrate the experiments with real mural conditions. Cleaning tests demonstrated promising removal efficiency, influenced by the chemical composition, thickness of the overpainted layers, and surface roughness. The reintegration system met the expected performance requirements, as the tested binders provided good results and allowed the development of compatible, reversible, and distinguishable solutions. Protective coatings showed good results in terms of chromatic stability and surface integrity; however, the long-term behavior of both reintegration, cleaning, and protection systems requires further evaluation. The results achieved so far support the development of sustainable and flexible conservation strategies for the conservation of contemporary street and urban murals and will guide the future application of the selected materials and methodologies in pilot conservation interventions on the mural chosen as a meaningful case study within the broader research.