The director is to base the action comedy on a script by Premium Rush writer John Kamps, which is still being developed, according to Deadline.
Spy vs Spy has been running in Mad magazine since the 1960s and is about the violent yet silent relationship between two spies, one who dresses in black and the other in white.
Howard was this week also linked to the Formula One film Rush, which focuses on the rivalry between 1970s champions Niki Lauda and James Hunt.
He is also reportedly submitting the first draft of his script for Stephen King adaptation Dark Tower to Universal this week.
In May, it was announced that the project was in doubt because of the studio's concerns about its cost, which would have included a trilogy of films and two television miniseries.