Industry sources have indicated that director Shawn Levy (Night at the Museum) has arranged a meeting with the Men in Black star in hope of signing him to the project, according to The Hollywood Reporter.
Fantastic Voyage is a re-imagining of a 1960s film that centers on a crew of scientists who are shrunk down to the sizes of atoms and sent into another scientist's body via a miniature submarine in an attempt to save his life.
Director Paul Greengrass was originally attached to the project, but ultimately elected to leave the film in favour of Warner Bros's adaptation of the Robert Louis Stevenson novel Treasure Island.
Levy is reportedly now facing a similar dilemma about whether or not to stick with the movie, as the project has been held up by casting difficulties. However, insiders claim that if Smith signs on to the project, the film will almost certainly move forward.
James Cameron is producing the reboot with his Lightstorm Entertainment partner Jon Landau.
Smith is said to be planning a return to rap music, with producer La Mar 'Mars' Edwards indicating that the actor is heading back to the studio to record a fifth solo LP.
The actor recently acquired the rights to Kazu Kibuishi's Amulet series.
The original Fantastic Voyage movie featured Edmond O'Brien, Raquel Welch and Stephen Boyd.