After moving to Athens in the early 1990s, Vandi signed with Minos EMI and released two albums Gela Mou (1994) and Esena Perimeno (1996).

She then began an exclusive collaboration with songwriter/producer Phoebus and achieved commercial success with her third album, Deka Endoles (1997), followed by the multi-platinum Profities (1999), as she established a more "pop" stage performance style and image, becoming one of the most prominent artists of the laïko/pop genre.

Following Phoebus' departure from Minos EMI, Vandi followed him to the newly formed independent label Heaven Music and released Gia (2001), which became and remains her biggest commercial success, as well as one of the best-selling albums of all time in Greece and Cyprus.

[2] In 2007 10 Hronia Mazi, a ten-year celebration of her collaboration with Phoebus was released, followed by her eighth studio album C'est La Vie.

Phoebus wrote the songs of Vandi's next album, Deka Entoles (Ten Commandments), which was certified double platinum and sold 100,000 copies in Greece.

[20][21] In 2001 Despina Vandi and Phoebus signed in with Heaven Music, a new break-out record label, owned by the Antenna Group.

In the meantime, with Gia having been certified multi-platinum in Greece and Cyprus, some of the songs broke out into the international market in neighboring countries.

The song Gia gave to her the award for the best dance artist for the year 2004 in Portugal and she makes a big concert for her European public.

[29] In the first days of October 2004 Despina Vandi makes four big concerts in New York, Atlantic City, Chicago and Toronto.

[29] Vandi also made an appearance on the hit international show Top of the Pops where she performed her song "Gia" as she was included in some of that week's best-selling popular music artists.

[citation needed] Vandi's work has been remixed by celebrated global DJs and producers, such as Armand Van Helden, Milk & Sugar, Nick Skitz, Roger Sanchez, Junior Vasquez, Pete Tong, Bass Bumpers, DJ Gregory, Level K, XTM, Minimal Chic and Highpass amongst others.

[citation needed] Vandi's next studio album was released at the end of 2004, titled Stin Avli Tou Paradisou (In The Garden of Paradise).

[36] The second single from the album and the title track "10 Hronia Mazi" (10 Years Together), a rock ballad celebrating the 10-year collaboration with Phoebus, was released on 16 November 2007.

[citation needed] Vandi was featured on the gold-certified album Sehnsucht by German electronica act Schiller, which was released in early 2008, providing vocals for the song "Destiny", composed by Phoebus.

[43] In the end of 2008, Vandi began an international tour and on 10–12 October she performed three sold-out concerts in Melbourne, Sydney and Adelaide.

[45] On 16 June, Vandi made a dynamic comeback, after a year's absence, with the pop-rock song Iparhi Zoi (There's still life).

In 2010 Vandi presented her new song, "Koritsi Prama", exclusively for the listeners who wοn VIP invitations from Dromos 89.8 FM radio.

[54] "Koritsi Prama, Part 1", was released on 22 March and was the lead single from her eighth studio album, "C' est la vie".

[60][61] It was her first album to be released along with a newspaper, following a popular tendency of the Greek musical industry, as an effort to deal with the reduction in the disc sales.

On 14 June, Vandi performed live at the MAD Video Music Awards, presenting her new song "Kommati Ap' Tin Kardia Sou".

[72][73] On 14 June 2011 Despina Vandi appeared on Mad Video Music Awards 2011 and performed the song "Gi' Alli Mia Fora" (For one more time).

In November 2011 a digital single was released by Vandi called "Mou 'His Perasi", as a promo to Despina's forthcoming album.

On 15 January 2013 the Hellenic Broadcasting Corporation (ERT) announced that it had reached an agreement with private music channel MAD TV to take on the organisation and production of a national final to select a song to represent Greece in the contest.

On the meantime Despina's digital single Hano Esena produced by Dimitris Kontopoulos was released on 2013, receiving positive reviews and remaining 10 weeks at the top of the airplay chart.

Instead, she collaborated again with various songwriters, among them: Dimitris Kontopoulos, Eleni Giannatsoulia, Olga Vlahopoulou, Giorgos Sampanis, Nikos Moraitis and Vasilis Gavriilidis.

Vandi collaborated again with various songwriters (among which Dimitris Kontopoulos, Thanos Papanikolaou, Nikos Moraitis, Eleni Giannatsoulia, Vasilis Gavriilidis, Olga Vlahopoulou).

Her eleventh album features the following singles: 'Mia Anasa Makria Sou', 'O,ti Thes Geniete Tora', 'Gia Kaki Mou Tihi'.

Inspired by the musical, she released the album "To Diko Mou Cinema" (2019), including covers of notable songs from popular Greek films produced in the 1960s and 1970s.

Vandi visits a variety of Greek towns and villages showcasing their traditions, culture, local food, and history.

Living in a lower-middle-class family, her dream was to become either an actress or a singer but she always knew that she should have something more solid as a background so she went on to study psychology, philosophy, and education at the University of Thessaloniki.