Zoku Natsume Yuujinchou follows Takashi Natsume, a young boy who has been able to see youkai since he was young, and his protector, the youkai named Nyanko-sensei. Takashi's goal is to return the names listed in his late grandmother Reiko's "Book of Friends" to their rightful youkai owners within his village. Throughout the journey, Takashi encounters different types of youkai - kind-hearted ones, those attempting to steal the book, and even murderous ones - all while discovering more about himself and his connection with these enigmatic beings. This plot is reminiscent of its predecessor.