Nanette Lepore moved from Ohio to New York City, where she began to develop her professional career as a designer. She attended New York's Fashion Institute of Technology and graduated with a degree in design. Prior to moving to New York City, Nanette also earned an undergraduate degree from Youngstown State University.

Nanette Lepore gained celebrity in the fashion world after she returned to California, opening a boutique store in Los Angeles and selling her outfits to clients in Europe and Asia. She also began to have her items featured in the famous American store chain, Neiman Marcus. She also gained renown for her flair on the runway and began to attract stars like Aida Turturro, Illeana Douglas, Lorraine Bracco, Eva Longoria, Kerry Washington, and America Ferrera.

She also has her own fragrance named Nanette.

In spring 2007, Nanette Lepore launched a collection of shoes with Keds. Mischa Barton was the face of the line.

In 2013 Lepore participated in Levo League's live business leader Q&A series, "Office Hours", to share advice with the site's community of young professionals.

Today, Nanette Lepore is sold across America, including Saks Fifth Avenue, Neiman Marcus, and Macy's. She has boutiques in Chicago, Boston on Newbury Street, New York in Soho and Madison Avenue, Los Angeles on Robertson Boulevard.

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