Sigismondi's first feature-length film is The Runaways, a period piece about the 1970s all-girl rock and roll band The Runaways. The film is largely about the relationship between Joan Jett (played by Kristen Stewart in the film) and Cherie Currie (played by Dakota Fanning). Sigismondi wrote the screenplay based on Currie's book Neon Angel: A Memoir of a Runaway. The film premiered in 2010 at the Sundance Film Festival and was released in Canada and the United States in March 2010. In an interview with Exclaim!, Sigismondi said "I went in and said I didn't want to make this a straight-up biography. I want to make this a coming of age, because that's what's so interesting about them. And if you want to compare them to anybody else, that's what makes them so special, is how young they were, and that they were all female. So those kinds of things really resonated with me." Her next feature film project is directing Alejandro Jodorowsky's Bouncer, and she is currently in development on a dark comedy titled Dave.

Sigismondi was born in Pescara, Pescara, Italy. Her parents, Lina and Domenico Sigismondi, were opera Singers. Her family, including her sister Antonella, moved to Hamilton, Ontario, Canada when she was two. In her childhood she became obsessed by drawing and painting. Later, from 1987 she studied painting and illustration at the Ontario College of Art, today's Ontario College of Art & Design University (OCADU). When she took a photography course, she became obsessed once more, and graduated with a photography major.

With her photography and sculpture installations she had solo exhibitions in Hamilton and Toronto, New York City, Brescia, Italy, Gothenburg, Sweden and London. Her photographs also were included in numerous group exhibitions, together with artists such as Cindy Sherman, Joel-Peter Witkin, and Francesco Clemente. The German art press Die Gestalten Verlag has published two monographs of her photography, Redemption (1999) and Immune (2005).

In October 2004 she gave birth to a daughter, Tosca Vera Sigismondi-Berlin. Sigismondi resides in Toronto, New York City, and Los Angeles. Her daughter is named after the Italian opera Tosca. Floria herself was named after the main character.

Floria appears in the Canadian documentary films Flicker and Cinéma Vérité: Defining the Moment. Floria is a two time MVPA winner of Director of the year in 2006 and 2013. In 2013 Floria's directed video for Justin Timberlake "Mirrors" won video of the year at the MTV Video Music Awards.