Alessandra Mastronardi made her television debut in 1997 in an episode of the Italian miniseries ‘Un prete tra noi’. She subsequently appeared in the series Amico mio 2 (1998) and Lui e lei 2 (1999), and made her first film appearance in ‘Il manoscritto di Van Hecken’ (1999). After appearing in a guest role on the television series ‘Un medico in famiglia’ in 2001, she was cast in the short comedy film ‘Cose che si dicono al buio’ in 2004. The following year, she bagged the role of Rosa Di Girolamo in Claudio Bonivento’s made-for-television sports drama film ‘Il Grande Torino’ and also appeared in the TV movie ‘Il veterinario’, apart from a cameo appearance in the mystery drama film ‘La bestia nel cuore’ (‘Don't Tell’).
The first major role for Mastronardi was of Eva Cudicini in the television series ‘I Cesaroni’ (2006-12), which she portrayed both as a main and recurring cast for 105 episodes of the series over five seasons. Also in 2006, she appeared in an episode of the crime comedy series ‘Don Matteo’ and featured in the music video of the song ‘Stai bene come stai’ by Italian rock band Le Mani, which was the winning video at the ‘Italian Videoclip Award 2007’. In January 2007, she made her stage debut at the Teatro de 'Servi in Rome with the comedy ‘The Prozac Family’, which was later revived at the Parioli Theater in 2009. She played the role of Gloria in Lorenzo Cicconi Massi’s debut film ‘Prova a volare’ (2007), which was produced in 2003 under the name ‘Il motore del mondo’. In 2008, she returned to television in the main role of ‘Roberta Vannucci’ in the series ‘Romanzo criminale - La serie’, based on the novel of the same name by judge Giancarlo De Cataldo. In the following years, she appeared in several TV movies including ‘Non smettere di sognare’ (2009) – in which she played an important role of a young dancer named Stella Carossi, as well as ‘Sotto il cielo di Roma’ (2010) and ‘Atelier Fontana - Le sorelle della moda’ (2011). She also acted in the short film ‘Il fidanzamento di mia madre’ in 2011.
Mastronardi gained international recognition in 2012 after portraying Milly, a young bride and astronomy teacher, in Woody Allen’s magical realist romantic comedy film ‘To Rome with Love’, which earned her a nomination at ‘Nastro d'Argento’ for ‘Best Supporting Actress’. Her television credits that year included the role of copyist Sofia Silvestri in the international history drama miniseries ‘Titanic - Birth of a legend’ and Clelia Conti in the two part miniseries ‘La Certosa di Parma’. In 2013, she starred in the English-language Italian comedy film ‘AmeriQua’ (‘Eurotrapped’), also starring Alec Baldwin, and the Italian comedy drama film ‘L'ultima ruota del carro’ (‘The Fifth Wheel’), which was the opening film at the ‘2013 Rome Film Festival’. She played Giulietta (Juliet) in the 2013 telefilm ‘Romeo and Juliet’ and reprised the role in the two-part miniseries of the same name the following year. In 2014, she further starred in two successful comedy films, ‘Amici come noi’ and ‘Ogni maledetto Natale’, and appeared in the short film ‘Un'altra storia’. That year, she also shot for the Italian-American romantic drama film ‘The Tourist’, directed by Evan Oppenheimer, but it was released much later in 2017 with the title ‘Lost in Florence’.
In 2015, Mastronardi appeared in the English-language international biographical film ‘Life’, starring Robert Pattinson and Dane DeHaan. The following year, she acted in the Polish adventure crime thriller ‘Titanium White’ and bagged the lead role of Alice Allevi in the Italian television series ‘L'allieva’, which she portrayed in 35 episodes for three seasons until 2020. In 2017, she was cast as Francesca in the second season of Netflix's American comedy-drama ‘Master of None’ and also appeared as Giulia Martini in the Italian miniseries ‘C'era una volta Studio Uno’. She subsequently played a supporting role in the 2018 English-language Italian fantasy adventure film ‘C'era una volta Studio Uno’ and played the main role of Lucrezia Donati in the second and third seasons of the Anglo-Italian historical drama series ‘Medici’ (2018-19). Since then, she has played major roles in a number of movies such as the Italian comedy films ‘L'agenzia dei bugiardi’ (2019), ‘Si muore solo da vivi’ (2020), ‘La donna per me’ (2021) and ‘Con chi viaggi’ (2022), the American romance film ‘About Us’ (2020), the American crime comedy ‘The Unbearable Weight of Massive Talent’ (2022) starring Nicolas Cage and Pedro Pascal, and the Italian action comedy ‘Altrimenti ci arrabbiamo’ (2022). Moreover, she portrayed Italian ballet dancer Carla Fracci in the 2021 biographical telefilm ‘Carla’ and appeared in several music videos by artists like Gianni Morandi (‘Dobbiamo fare luce’), Jack Savoretti (‘What More Can I Do?’), and Francesco Gabbani (‘La mira’).
The film presents four unrelated stories, taking place in Rome. The first story focuses on an Italian bathroom singer being put on stage by an American opera director, while the second portrays the perils of a young couple, fresh from rural belt. The third focuses on a middle-class Roman suddenly becoming a celebrity while the fourth is about an American architect reliving his youth.