The following version of the book was used to create this study guide: Bayron, Kalynn. This Poison Heart. Bloomsbury Publishing, New York, NY, 10018, 2021. Kindle AZW file.

As the novel opens, Bri Greene is living with her two adoptive mothers, Thandie and Angie, in Brooklyn. Bri's life is nothing close to a normal teen's life because she spends a lot of time and energy trying to manage her supernatural power to control plants. As she walks down a sidewalk, the trees and plants along the street bend toward her. The plants in her room react to her mood. Bri knows that money is tight. She discovers that they are on the verge of being forced to move to a smaller apartment just when an attorney named Mrs. Redmond arrives with news that Bri's biological aunt, a woman named Circe Colchis, left Bri a house and 40 acres of land near Rhinebeck in upstate New York. Though worried about the effect of being in the middle of a forest, Bri and her mothers agree to spend the summer at the house to see if this could be the answer to their financial problems.

Bri quickly feels a connection to the house and to the many paintings and pictures of people displayed on the walls. The house includes a huge room set aside as an apothecary, complete with jars of dried herbs on the shelves. She soon discovers a hidden garden behind a gate covered with plants. The plants clear the way for Bri but attack others who try to reach the garden. Though neglected, the front part of the garden is filled with the typical medicinal garden herbs. Behind a locked fence, Bri finds the Poison Garden with deadly plants such as oleander. She has no fear, having already discovered she is immune to poisonous plants of all kinds. There is a locked room past these poisonous plants, and Bri eventually finds the key that unlocks the door. Inside, she finds a plant that she had assumed was not real – Absyrtus's Heart. The plant is in the dark, and its stems and leaves are dark and wilted.

Bri begins to make some friends around town. Karter is Mrs. Redmond's son. He seems kind in a clumsy and distracted way. The mysterious Marie, who lives in an elaborate house, mentions a connection to Bri's family. Eventually, Bri discovers that Marie has been alive for hundreds of years because of receiving an elixir containing Absyrtus's Heart. Karter's mother is trying to steal the heart so that she will become immortal. Bri is devastated to learn that Karter has been helping her.

Mrs. Redmond holds Thandie at knife point, forcing Bri to retrieve the Absyrtus's Heart plant. Mrs. Redmond then forces the poisonous oleander into Thandie's mouth, killing her almost instantly. Ange arrives followed by Hecate, Medea's mother. Hecate drags Mrs. Redmond into the underworld and orders Karter to never return. Bri pleads for her mother's life. Hecate says Thandie is dead, but Bri can save her if she reunites all six of the Absyrtus's Heart plants originally left in the care of Bri's family. As the novel ends, Hecate takes Thandie to the underworld, saying Bri has a month to gather the plants. Circe arrives, revealing that she did not die after all.