The Blue Bloods alum, 41, will play Calista Raines, a creative director of a luxury fashion brand. She's described as being "uber-fabulous" and having a "larger-than-life" personality. Under the surface, however, she's lonely and has a "darker, more devious nature."
Milano surprised fans when she announced her departure from the ABC drama after two seasons back in October, citing her inability to move to the show's new Canadian shoot location.
"After two wonderful seasons in Los Angeles, the studio has decided to shoot season three of Mistresses in Vancouver, Canada for financial reasons. It's with a heavy heart that I have decided that I can't relocate," the Who's the Boss? alum, 42, wrote on her personal site.
"I have two babies under 4. Being a mother and wife comes first and I just cannot uproot my children and separate the family by moving away," she continued. "I will miss this job desperately and wish everyone the absolute best."
Milano and CAA agent husband David Bugliari share daughter Elizabella, 5 months, and son Milo, 3.
Esposito is best known for her TV roles in Judging Amy, Samantha Who?, Blue Bloods, Taxi Brooklyn, and 2004's Oscar winning film Crash. In November 2012, Esposito spoke out about her abrupt dismissal from CBS' Blue Bloods. At the time, she was ordered to go on medical leave while she was treated for celiac disease.
"After a week off, my doc said I could return to work but CBS implied that I was not truly ill and this was a scheme to get a raise!" she tweeted at the time. In an interview with FOX News, she added: "Last week I was told I was on suspension, which meant I am still in contract, not being paid. It's completely illegal, but they also knew that I didn't have the money or the means to sue them."
In lighter and more personal news, Esposito wed longtime love Louis Dowler (the British male model once dated Kate Winslet) in November 2014. She split from Bradley Cooper in November 2007 after four months of marriage.