Santoro initially developed a literary practice in Italian (his parents emigrated from Sicily, Italy, to Switzerland before his birth.) In 1985, he published the collection of poems entitled La Voce e le Mani, Progetto per una poesia inumana (Lalli Editore, Poggibonsi). His work with the medium of language continues to this day and was even reinforced after meeting with artist Jenny Holzer in the early 1990s. In the mid-1990s, he increasingly turned to photography as a means of expression. In close collaboration with the American writer Paul Bowles, he publishes The Time of Friendship / Ten Photographs (Memory/Cage Editions, Zurich, 1995). He then gradually expanded the spectrum of media towards sculpture, installation and video/film. Images, space, signs, sounds and language are intertwined in works such as F. Dostoyevsky: C. and P., Page 67 (Penguin Popular Classics), divided vertically, 2007/2011, Untitled (Mask), 2007, Monologism As Poetry, 2009, Reciprocal Scrutiny (bordereau), 2009, Gagarin, I-II, 2012, Good-bye Darkness, IV, 2010, and In/Voluntary Movement Diagram (Josef K.), 2014.
His works are based in everyday observations, but go beyond them to show latent historical, aesthetic, sociopolitical, or even metaphysical realities. His characteristically intricate visual sensibility conceals a tension between the referential possibilities of objects and the choreographic nature of their placement in context. For each work Santoro chooses specific ways to manipulate conventions to desired effects believing that creativity is an ongoing process of continual change and reaction.
In an artist statement for the installation Reciprocal Scrutiny (bordereau), 2009, shown at Galerie Xippas in Paris, the artist has stated: “I like to think that the different elements of the work will serve as triggers and incite the viewer to form connections between the literary, political, historical and perceptual sources. And, furthermore, encourage a rigorous parlay between one’s own subjectivity and an ‘impassive’ art object. This interplay between abstract data, geometric and linguistic forms, historical facts and fictional information can be negotiated and interpreted in any number of ways. I would enjoy that the piece would dilate like a web of associations, interferences and allusions. The center of the project space remains empty and my interest is to explore what, in this vacuum, might now be possible.” 
His work is represented by Galerie Thomas Bernard-Cortex Athletico, Paris, and Counter Space, Zurich.