Revealed in Japan's Famitsu magazine, the title will be Mikami's return to making a survival horror game. His last game in the genre was 2005's Resident Evil 4.
A teaser image for the game was posted on the Tango Gameworks website, featuring a collage of concept art conveying a foreboding atmosphere.
Tango Gameworks was founded by the Resident Evil and Phoenix Wright creator after leaving Platinum Games in 2010.
The studio was then purchased by Bethesda parent company Zenimax, who will be the publisher for Zwei.
Back in 2010, Mikami said that his next game with Tango Gameworks would be his last in a director role.
Mikami also collaborated with Grasshopper Manufacture to create last year's horror comedy Shadows of the Damned.
Zwei is slated for a 2013 release, but no platforms have been specified at this time.
Watch the latest trailer for Resident Evil 6 below: