Her international breakthrough happened in 1984 with the release of her sixth album, the Conny Plank-produced Puzzle, which peaked in the top 10 in the Italian, German, Austrian and Swiss charts.

Nannini embarked on a long European tour to support the album, culminating in a headlining gig at the Montreux Jazz Festival.

In 2004, she released the greatest hits album Perle, where a number of her most renowned songs were rearranged with the support of musicians such as Christian Lohr on piano (who also had a co-producer credit), and a string quartet composed of Vincenzo di Donna (first violin), Luigi de Maio (second violin), Gerardo Morrone (viola) and Antonio di Franca (violoncello).

In 1987, she performed with Sting, Jack Bruce and Eberhard Schoener the "Three Penny Opera" by Bertolt Brecht and Kurt Weill at the Schauspielhaus in Hamburg.

Nannini was also featured on Einstürzende Neubauten member Alexander Hacke's solo album Sanctuary, on the track "Per Sempre Butterfly".

[4] Nannini's pregnancy was prominently featured on the cover of Vanity Fair, where she was portrayed wearing a T-shirt with the inscription "God is a Woman".

In her 2017 autobiography, entitled Cazzi miei, she revealed she was ready for a civil union with Carla, explaining she felt Italian laws could not give her any guarantee about Penelope's future in the case of Nannini's death.