In the Joseon period. Rumours start to circulate that the king has died from smallpox after he falls ill. The Haewon Cho Clan labels Crown Prince Lee Chang a traitor. This clan is the clan of the current pregnant queen and her father, Cheif state councilor Cho Hak Joo. The Crown Prince, along with his guard, thMoo Young to find out the truth about his father's death, travels to Dongnae with his guard to search for Physician Lee Seung Hui, who treated his father. However, he is left with Assistant Physician Seo Bi, Young Shin and a mysterious man called Young Shin in a village with mysterious diseases. The second season focuses on the spread of plague in several provinces. Sangju is the scene of a shocking revelation in the days leading up to the end of the plague outbreak. The arrival of winter means that the undead hordes can now freely roam the earth due to the change in the ambient temperature. Prince Lee Chang is afraid of the consequences of an invasion and seeks support from his friends to stop them. The corrupt Haewon Cho Clan is plotting another conspiracy to gain political power, unbeknownst the Prince. To cement her position as queen consort Cho, she plans to steal a male infant to secure her heirship to the royal throne. She also orchestrates a last-ditch strategy to use plague to attack the Hanyang citizens if her previous plan fails. Only one question remains as calamity threatens the living. Will the plague bring an end to the Joseon dynasty or can the Prince save his people?