Some of Chappell's and Leccia's former Guiding Light co-stars also appear in the series, including Tina Sloan, Gina Tognoni as Sami and Jordan Clarke as The Colonel.

Other Venice cast members include daytime actress Hillary B. Smith of One Life to Live as Guya, Nadia Bjorlin as Lara, Galen Gering as Owen, Gina's brother, Michelle N. Carter as Michele, Lesli Kay as Tracy, Michael Sabatino, Chappell's husband, as Alan, and Robert Newman as an old boyfriend of Gina's.

Other cast members include Shawn Christian, Eric Martsolf and Molly Burnett from Days of Our Lives.

Crystal Chappell played Olivia Spencer on the long-running CBS daytime drama, Guiding Light, from 1999 until the September 18, 2009 network ending.

In 2009, after Guiding Light was cancelled, Chappell, with help from her writing partner and co-producer Kim Turrisi, decided to create Venice: The Series drawing inspiration from the popular romance between her Guiding Light character, Olivia Spencer, and GL co-star Jessica Leccia's character, Natalia Rivera Aitoro, also known by the portmanteau "Otalia".