"Lullaby to the Big Sleep" is a psychological thriller set in a dystopian future where humanity is plagued by a mysterious phenomenon known as the "Eternal Slumber." This condition causes individuals to fall into an irreversible coma, leaving their bodies alive but their minds trapped in an endless dreamscape. The story centers on Akira Tachibana, a young neurologist who specializes in dream analysis, and her team of researchers tasked with uncovering the cause of the phenomenon and finding a cure.

Akira discovers that the comatose patients share a recurring dream motif—a haunting lullaby that seems to guide them deeper into their subconscious. As she delves further into her research, Akira begins to experience fragments of the same dream, blurring the line between her reality and the dream world. Her investigation leads her to a clandestine organization known as the Somnus Foundation, which has been secretly experimenting with dream manipulation technology. The Foundation's leader, Dr. Renji Kuroda, reveals that the lullaby is a byproduct of their attempts to control human consciousness, but the experiment spiraled out of control, triggering the Eternal Slumber.

The narrative explores the ethical dilemmas of tampering with the human mind, as Akira and her team race against time to reverse the effects of the lullaby. Along the way, they encounter other key figures, such as Haruto Saito, a former Somnus researcher turned whistleblower, and Yuna Mizushima, a comatose patient whose dreams hold the key to understanding the lullaby's origins. The story intertwines their personal struggles with the larger mystery, creating a tense and layered plot.

As Akira ventures deeper into the dreamscape, she uncovers a hidden truth: the lullaby is not merely a tool of control but a manifestation of humanity's collective unconscious, reflecting fears and desires buried deep within the psyche. The climax sees Akira confronting the source of the lullaby within the dream world, forcing her to make a choice between eradicating the phenomenon entirely or finding a way to coexist with it. The series concludes with an ambiguous resolution, leaving the fate of the dreamers and the world open to interpretation.