When he returned to Italy in 1949, he began his polemic against criticism for an all-out reading of Futurism and, at the end of 1950, he launched the Manifesto of painting and nuclear plastic. In 1951 he participated in the IX Triennale di Milano with a personal room, in 1952 he was present in the hall of the masters at the XXVI Biennale di Venezia, in 1955 at the VII Quadriennale di Roma and, finally, in 1959 at the commemorative exhibition for the fifteenth anniversary of the first Futurist manifesto.
Between 1953 and 1956 he realized the great preparation and furnishing of the Provincial Council Hall in Trento and, finally, in 1957 he started the creation of his museum, the very first Futurist museum, which was inaugurated in August 1959, when he was already undermined by the illness. A little over a year later, on October 29th, Depero died without a clamor, leaving the city of Rovereto with a donation of over three thousand works of art but also with the commitment to enhance his painting in the future. His faithful wife Rosetta, director of the tapestry workshop, joined him in 1976.