With the help of the "Dragon Sin of Wrath" Meliodas and the worst rebels in history, the Seven Deadly Sins, the "Holy War", in which four races, including Humans, Goddesses, Fairies and Giants fought against the Demons, is finally over. At the cost of the "Lion Sin of Pride" Escanor's life, the Demon King was defeated and the world regained peace. After that, each of the Sins take their own path.

Dr. Lily Houghton enlists the aid of wisecracking skipper Frank Wolff to take her down the Amazon in his dilapidated boat. Together, they search for an ancient tree that holds the power to heal – a discovery that will change the future of medicine.