Letizia Gambi was born in Naples into a theatrical family; her uncle is an opera singer and her brother, Gianpaolo Gambi, is an actor, television host and writer. The family moved to Como, where she studied art and dance, and she later went to Milan to study acting and singing, graduating from Milan's International Jazz School with a master's degree in jazz vocal performance. She has been active professionally since 2003 and sings in English, Italian, Neapolitan and Spanish. Her birth date is not publicly documented.

The turning point came in 2009, when she met the drummer and producer Lenny White at the Blue Note in Milan, where he was playing with Chick Corea and Stanley Clarke. The same year she lost all hearing in her right ear to sudden sensorineural hearing loss, a condition she has discussed in Italian press interviews and one that did not stop her singing career. White produced her debut, Introducing Letizia Gambi (Jando Music, September 2012), which Discogs files as a Jazz album in the Vocal and Contemporary Jazz styles. It mixes Neapolitan standards such as "'O Sole Mio" and "Passione" with English-language originals, a Björk song ("Bachelorette"), a Lucio Battisti pop song ("E Penso a Te"), and a medley that folds the Neapolitan "Munasterio 'e Santa Chiara" into Duke Ellington's "In a Sentimental Mood." According to the label's release materials and reviews, the guests included Chick Corea, Gato Barbieri, Wallace Roney, Patrice Rushen, Gil Goldstein and Ron Carter, though Discogs itemizes only White's producer credit. The record was reviewed by JazzTimes and Jazzwise, and her official biography says it was entered in the first round of Grammy balloting.

Her second album, Blue Monday, came out on ArtistShare in February 2016, again produced by White, who also plays drums. It is the release where the personnel can be confirmed most fully at the Discogs credit level: Ron Carter on bass for three tracks, John Benitez on bass for six others, pianists Helen Sung and Donald Vega, Gil Goldstein on accordion, guitarist Dave Stryker on one track, and cellist Jisoo Ok. The repertoire runs from "Sweet Georgia Brown" and "But Not For Me" to Amy Winehouse's "Back To Black," song titles that pair English and Neapolitan ("Without You / Senz'e Te"), and originals credited to Gambi and White. AllAboutJazz, Jazzwise and the Latin Jazz Network all reviewed it, DownBeat profiled her in its June 2016 issue under the title "Cross-Cultural Mix," and the album drew a Premio Tenco nomination in Italy. She also received the San Gennaro Award in Naples in 2016.

Later work has been smaller in scale and more varied. She sang with the Alfredo Rey Orchestra in 2004 (backing vocals on Alta Infedeltà), recorded "Dindi" with White for the Musica Jazz tribute compilation 100% Frank (1915-2015 Tribute To Sinatra), and put "Back To Black" on a 2016 JAZZIZ On Disc sampler. In 2018 she formed the all-female group Letizia Gambi in 3D with pianist Elisabetta Serio and cellist Giovanna Famulari, later adding a drummer; the quartet made its debut on International Jazz Day 2021 at Blues Alley in Washington, D.C. In 2020 she wrote the Italian lyrics for and sang "Come musica" on the pianist Fahir Atakoglu's album For Love. Her official biography also lists a Rai 2 television celebration of Pino Daniele's 70th birthday, two theatrical productions she created (A Neapolitan in New York and Womanity), and a Spanish-language project and a libretto for a symphonic opera by White in development. She has been a Recording Academy voting member since 2012 and lives between New York and Miami.

Gambi's approach is to treat Neapolitan song as jazz repertoire and to set it beside American standards, often in English versions. One reviewer describes her as a contralto, and her arrangements put Italian and Neapolitan melodies over the harmonic language and rhythm-section feel of the New York jazz scene of White and Carter. English translations of Neapolitan classics are a recurring device. Wikipedia lists traditional pop, world music and easy listening alongside jazz as her genres, and her career includes television and theater work outside the jazz clubs, but her recordings are filed as jazz on Discogs, her albums were reviewed in jazz-specific outlets (AllAboutJazz, Jazzwise, JAZZIZ, DownBeat, Musica Jazz), and the Discogs-listed sidemen on Blue Monday (Carter, Sung, Vega, Goldstein, Stryker) are all working jazz musicians.