The Game is a term that will tend to be used for any very important game, such as the Super Bowl, or an annual football contest between Harvard and Yale, disputed at each school's stadium in alternate Novembers, or other such important events. (For an article regarding the Harvard-Yale football game, see The Game (college football)). Usage will of course vary, as is the nature of the term, much like "the City" which depending on the location may refer to New York City, Washington, DC, Paris, San Francisco, etc.
The Game is a sort of giant treasure hunt played on several college campuses
The Game is also the nickname of professional wrestler, Triple H.