In an elegant Spanish-style apartment complex in the trendy Melrose neighborhood of Los Angeles, the lives and relationships of a diverse group of 20-somethings intertwine to form a close-knit surrogate family. Sydney Andrews (Laura Leighton, the original "Melrose Place") is the landlady, still beautiful at 40, and a central figure in the lives of all her tenants, especially handsome and rebellious David Breck (Shaun Sipos, "Shark"). Sydney started an affair with David despite her turbulent history with his estranged father, Dr. Michael Mancini (Thomas Calabro, the original "Melrose Place"). Both father and son learned through experience that Sydney was not above using blackmail to control people.

Another tenant, high-powered publicist Ella Simms (Katie Cassidy, "Supernatural"), once considered Sydney her mentor, but their friendship was destroyed by betrayal, and Sydney threatened to evict Ella and ruin her career. Sydney also played a pivotal role in the career of Auggie Kirkpatrick (Colin Egglesfield, "All My Children"). After they met at an AA meeting, she became a supportive friend to Auggie and encouraged his dream to become a chef. He’s now a successful sous chef at the trendy restaurant Coal, but his relationship with Sydney has gone sour since she began drinking again.

The other tenants include Lauren Yung (Stephanie Jacobsen, "Terminator: The Sarah Connor Chronicles"), a medical student in desperate need of money to pay her student loans, and Jonah Miller (Michael Rady, "Swingtown"), an aspiring filmmaker who has just proposed to his live-in girlfriend Riley Richmond (Jessica Lucas, "Cloverfield"), a first-grade teacher. The newest tenant, wide-eyed 21-year-old Violet Foster (Ashlee Simpson-Wentz, "7th Heaven"), has just arrived in LA and is horrified to find a bloody body floating in the courtyard pool. David is the leading suspect but, as the police are soon to discover, almost everyone living at Melrose Place had a reason to want the deceased out of the way.