In the heart of Italy, the Social Welfare Agency rescues young girls from hospital beds and gives them a second chance at life using the latest in cybernetic advancements. With their artificially enhanced bodies, the girls are brainwashed and trained as assassins to carry out the dirty work of the Italian Government. Despite all the modifications, they are still just children at heart, struggling for recognition from those they love, even knowing the love they feel is manufactured. This tragic tale unfolds as these girls grapple with their emotions in an agency that treats them as nothing but ruthless killers.

After one of his coworkers fails to repay a debt, apathetic bum Kaiji Itou is pressured by loan sharks to settle the large sum of cash. Since Kaiji has little money and no future prospects of his own, he is unable to return what his colleague borrowed. Faced with massive financial burdens, Kaiji is given an offer to board the illustrious Espoir—it is said that one night aboard the ship, and all of your debts will be paid. What seems like a simple night of gambling quickly turns into a game of strategy and betrayal. With the losers of the tournament being subjected to a backbreaking life of indebted servitude, Kaiji must choose his actions—and allies—carefully. However, this is only the beginning of a series of gambles that will wager Kaiji's life, testing the full extent of his wits and will to survive.

Defense attorney Ryuuichi Naruhodou is still hard at work defending the falsely accused with his knack for last-minute turnabouts. With his trusty assistant and medium-in-training Mayoi Ayasato in tow, Ryuuichi's fame as a champion for the innocent steadily grows. But this newfound success attracts the attention of the coffee-loving, masked Godot⁠—a mysterious rookie prosecutor who bears an inexplicable grudge against Ryuuichi. With the help of their allies, Ryuuichi and Mayoi take this new challenger head-on and search for the reason behind his appearance. But before long, the first two cases from the career of Mayoi's late sister Chihiro Ayasato become critical to solving a fantastical murder mystery, continuing the bloody saga of the tumultuous Ayasato clan. Will Ryuuichi once again be able to overcome the odds and find the truths hidden within the web of lies?

Owing to an increasing debt, Kaiji Itou ends up resuming his old lifestyle. One day, while walking on the street, he stumbles upon Yuuji Endou, who is hunting Kaiji due to the money he owes to the Teiai Group. Unaware of this, Kaiji eagerly follows Endou, hoping for a chance to participate in another gamble, but soon finds out the loan shark's real intentions when he is kidnapped. Given that Kaiji is unable to pay off his huge debt, the Teiai Group instead sends him to work in an underground labor camp. He is told that he will have to live in this hell for 15 years, alongside other debtors, until he can earn his freedom. His only hope to put an early end to this nightmare is by saving enough money to be able to go back to the surface for a single day. Once he is there, he plans to obtain the remaining money needed to settle his account by making a high-stakes wager. However, as many temptations threaten his scarce income, Kaiji may have to resort to gambling sooner than he had expected.