Sandra Nettelbeck was born on 4th of April 1966 in Hamburg to actress Petra Nettelbeck and film critic, journalist and author Uwe Nettelbeck. She gained her first film experience while still at school as production assistant to Heinz Emigholz, a friend of her father's, for his experimental film "Die Basis des Make-Up I" (1979-85. Emigholz introduced her to Elfi Mikesch and Monika Treut, who hired her as assistant director for their feature film "Verführung: Die grausame Frau" ("Seduction: The Cruel Woman", 1985).

In 1987, Sandra Nettelbeck started to study film at the San Francisco State University focusing on directing, screenwriting and production. She graduated in 1991 with the medium-length fiction film "A Certain Grace", which won the Audience Award for Best Short Film at the San Francisco International Lesbian & Gay Film Festival. She then returned to Germany, where she worked two years as an editor for Spiegel TV and Premiere TV.

Nettelbeck's first feature-length production was the relationship drama "Unbeständig und kühl" ("Loose Ends", 1995, TV) for which she also wrote the screenplay (as for all of her films) and played a small supporting role. Also for TV, she realized "Mammamia" (1998), a comedy film about various relationship and family conflicts starring Senta Berger, Christiane Paul and Peter Lohmeyer. The film won Best Picture and Best Screenplay at the film festival Max-Ophüls-Preis.

Her big breakthrough came in 2001 with her feature film debut, the international coproduction "Bella Martha" ("Mostly Martha"). The film stars Martina Gedeck as a head chef, who after her sister dies in a car crash is left to look after her 8-year-old niece and at work is confronted with a new team member, a charming Italian chef. The romantic comedy was an international box office success and won Nettelbeck as well as Gedeck several awards. Scott Hicks directed the Hollywood remake of "Bella Martha" called "No Reservations" with Catherine Zeta-Jones in the lead role.

In the meantime, Sandra Nettelbeck realized the children's film "Sergeant Pepper" (DE/GB/IT 2004) about the friendship between a 6-year-old boy and a dog. While "Sergeant Pepper" could win an award at the Munich International Film festival, it was not particularly successful at the box office. 

Nettelbeck's first English language film "Helen" (DE/CN 2009), starring Ashley Judd as a University professor suffering from severe depressions, premiered at the Sundance Film Festival. The film was nominated for the Preis der deutschen Filmkritik (Prize of the German Film Critics' Association) in the categories Best Picture and Best Screenplay.

"Mr. Morgan's Last Love" (DE/BE 2013), another English language production, was based on the novel by Françoise Dorner and was screened at several international film festivals. Michael Caine played the lead role of a British widower in Paris, who develops a special relationship with a younger woman (Clémence Poésy).

Nettelbeck then co-wrote a number of screenplays for films not directed by her, among them the much-acclaimed TV film about a surrogate mother, "Monsoon Baby" (2014, TV, Director: Andreas Kleinert), the box office success "Ich bin dann mal weg" ("I'm Off Then: Losing and Finding Myself on the Camino de Santiago", 2015, Director: Julia von Heinz; based on Hape Kerkeling’s bestselling novel of the same name) and the children's film "Hanni & Nanni: Mehr als beste Freunde" (2017, Director: Isabell Šuba).

In autumn 2016, Nettelbeck started shooting her next film "Was uns nicht umbringt" ("What Doesn’t Kill Us"). The ensemble comedy about a crisis-ridden psychotherapist (August Zirner) and his illustrious patients premiered at the Locarno Film Festival 2018 and was released in German cinemas in autumn of the same year.