The protagonist of the story is Maria Kunitomo, a rookie journalist working for Sakura TV station. One day she follows an interview with a renowned biologist, Dr. Amon, which captures her interest. Later that evening the news report that Dr. Amon has been killed in his laboratory, and his assistant, Jun Kageyama, whom Maria have met during the interview, is the prime suspect. While on a search for the truth behind Amon's murder, she stumbles on a conspiracy of a huge proportions.

It has been two years since the events in Maria: Kimitachi ga Umareta Wake, and while the setting is the same as well as some recurring characters, the stories are anything but connected. The gameplay is similar to its predecessor, using text-only during dialogue with characters while emphasizing key scenes with voice-acting and pre-rendered CG videos. Aside from direct dialogues in a visual novel style, Maria can use her computer and check emails to gather information. The game features three different endings available during first playthrough, after which the save game can be used to start new game which will open additional scenario routes and unlock two more attainable endings.