He sought to achieve these new environments with new materials, including fiberglass, ABS, PVC, and polyethylene. His Universale chair (1965) was one of the first to be manufactured from a single material. Other early commissions included the Impronta armchair (1961), the Acrilica lamp for O-Luce (1962), and the Roll chair (1962). His most unusual creations reflect his interest in modularity. His Mini Kitchen, exhibited in 1963 and manufactured by Boffi, housed a complete battery of cooking equipment and cutlery inside a small cabinet mounted on wheels. His Total Furnishing Unit (1969), an integrated living environment, combined all the amenities of a house, including a kitchen, bathroom, living and sleeping areas, divided into "functional stations". The Boby taboret (1970), another popular Colombo design, is still manufactured today by Bieffeplast.

By the time of his premature death from heart failure in 1971, Colombo had become a cult figure. He received the Compasso D'Oro in 1970, and the Total Furnishing Unit was posthumously exhibited at the Museum of Modern Art in New York.