Eni representatives signed the deal in Naypyitaw, the Myanmar capital, in the presence of government officials.
The exploration period will be divided into three phases over the next six years. The inland reserve areas cover a combined 3,000 square miles.
"This agreement marks Eni's first entry into Myanmar, a rapid expanding economy, and confirms its strategy to reinforce its presence in the South East Asia region," the company said in a statement Thursday.
Advocacy groups have expressed concern about the corporate interest in Myanmar given its human rights record. Sanctions on Myanmar eased when military rule ended in 2010, though rights groups say it was those sanctions that encouraged political reform.
In March, the country announced the results of a bidding round for energy contracts for offshore work.
The U.S. Energy Information Administration says Myanmar is producing few resources of its own, though output is increasing.