The novel revolves around the lives of the Lambert family, an old-fashioned midwestern couple and their three adult children. The parents, Alfred and Enid, are dealing with Alfred's Parkinson's disease and their own marital problems, while their children are each facing their own personal and professional crises. The narrative explores the themes of family dynamics, societal expectations, and the struggles of modern life. The story climaxes with the family's last Christmas together at their childhood home.

The novel explores the inner life and memories of a Midwestern woman named Janet, who is caught between her present life as a wife and mother and her past experiences growing up on a farm. On a fishing trip with a friend, Janet reflects on her youth, her relationships with men, and the complexities of her sexual awakening in a rural setting. The narrative weaves through time, revealing the quiet tensions and personal struggles that lie beneath the surface of her seemingly ordinary life, painting a poignant and introspective portrait of a woman's journey through the landscapes of her past and the emotional terrain of her inner world.

Margaret Anne "Moddie" Yance returns to her Midwestern hometown after a stressful decade in the city, seeking solace among old friends. As she navigates the complexities of rekindled relationships, Moddie finds herself entangled in a web of past grievances and new challenges. Her journey takes a turn when a mysterious artist arrives, forcing her to confront her past and reassess her life. Amidst parties and personal reckonings, friendships are tested, and Moddie must face the reality of her choices in this darkly humorous exploration of modern life.

In the small town of Monta Clare, the disappearance of teenager Joseph 'Patch' Macauley sends shockwaves through the community. His best friend, Saint Brown, is determined to find him, even if it means facing heartbreak. Patch, meanwhile, finds himself in a dark room, where he meets Grace, a mysterious girl who becomes his beacon of hope. When Patch escapes, Grace seems to vanish without a trace, leaving him with only her voice and name. Driven by memories, Patch embarks on a relentless quest to find her, while Saint pursues her own mission to uncover the truth behind their abduction. As time passes, their intertwined journeys reveal a tale of love, obsession, and the pursuit of justice, even if it means risking everything.

April and Eddie, a newlywed couple, accidentally find themselves on a deserted road while heading to their honeymoon destination. They encounter a mysterious hitchhiker who, after entering their car, reveals a chilling secret: she's injured and being pursued. When the hitchhiker dies at the hospital, April and Eddie become entangled in a series of unsolved murders along the road, drawing suspicion from the local police. Determined to clear their names, they delve into the town's eerie past and uncover a supernatural force that threatens to unravel the town's hidden truths and endanger their lives.

Quill, a Native American woman from the Red Pine reservation in Minnesota, is haunted by the past and determined to change the future. While training for a marathon, she hears a scream in the woods and discovers signs of a struggle. With the support of her friends and family, Quill embarks on a quest to uncover the truth behind the disappearance of a woman from her community. As she delves deeper, she confronts the harsh realities of life on the reservation and the systemic issues that allow such tragedies to occur. Quill's journey is one of resilience and determination as she seeks justice and strives to protect those she loves.

In the spring of 1919, John Sawtelle and his wife Mary embark on a journey to Wisconsin's north woods, accompanied by their friends and three dogs. Seeking a fresh start, they hope to find meaning and adventure in their new life. However, the challenges they face are more daunting than anticipated, requiring creativity and the help of new allies, both human and otherworldly. "Familiaris" explores themes of love, friendship, and the enduring bond between humans and dogs, set against the backdrop of historical events and personal quests for purpose.