Serena Depero was born in Rome, Italy, in 1974, and moved to New York City in 1988. She studied drawing at the Art Students League of New York, and then attended Brown University in Providence, RI, from where she graduated in 1995 with a BA in Visual Arts and Italian Studies. After college, she returned to the Art Students League to study mixed media with Charles Hinman and Bruce Dorfman. She then attended Hunter College and graduated in 2001 with a Master of Fine Arts in Painting.

A fascination with the materials themselves has been a driving force in all of her work. She constructs paintings using layers of color, which are applied based on a series of formal and intuitive choices. She often works and reworks a piece until each shape falls into place. Similarly, in her three-dimensional work, she recycles and transforms objects that she has an affinity for. The innate qualities of the materials help determine the final result. Nature and personal memories are a recurrent theme.

Depero has participated in numerous group exhibitions in the United States and abroad. She is part of a group of international artists called Across the Bridge, and a member of The Kingston Arts Society. She divides her time between New York City and Accord, NY.