The duo will appear in the film directed by the "50/50" filmmaker Jonathan Levine, reported Variety.
Rogen will essay the role of an unemployed journalist, who brings upon misfortune on himself through his self-destructive ways, while Theron will play his childhood crush and nanny whom he tries to pursue.
Things get difficult for Rogen's character as she now happens to be one of the most powerful and unattainable women on earth.
The script has been penned by veteran comedy scribe Dan Sterling.
The film is expected to start production in August.