Matilda "Mattie" Cook is a fourteen-year-old girl living above a coffeehouse in Philadelphia with her mother, grandfather (a former military man), a parrot named King George, and an orange cat named Silas. Eliza, a free black woman, is the coffeehouse cook. A typical teenager, Mattie is always in the middle of daydreams, beginning to notice boys and getting into all kinds of arguments with her single mother, Lucille. (Sounds like some things never change.)
One day, the coffeehouse's serving girl, Polly, doesn't show up for work. Turns out she came down with a case of the fever, and the next thing you know, she's being buried. Scary, right? Matilda sure thinks so. More and more cases of the fever start popping up, and rumors of an epidemic spread through the coffeehouse and across the city. Around this time, we're also introduced to the ever-so-dreamy Nathaniel Benson, a painter's apprentice, who Matilda runs into at the marketplace. The two have been friends for a long time, but Matilda is starting to see the chap in a whole new, hearts-and-flowers kind of light.
Anyhow, Matilda's very own mother, Lucille, is the next person to fall ill. One doctor after another visits the coffeehouse and, soon enough, they start draining her blood in an effort to cure her. (An unfortunate practice popularized, as we learn, by the physician Benjamin Rush.) During the illness, Matilda's mother demands that her daughter be removed to the country to avoid becoming infected with yellow fever too.
To please Lucille, Matilda and her grandfather set off for the safety of the country in a wagon with a farmer and his family. When they get stopped by town guards, though, Matilda and her grandfather are mistaken for fever patients and booted from the wagon. Not even the farmer and his family will come to their rescue! (It's every family for themselves, apparently.) Abandoned in the country, Matilda tries to care for her ailing grandfather (he's not in good shape, but doesn't have yellow fever), but falls ill herself with the fever herself. She starts to feel dizzy, and the next thing you know, everything goes black.
When Matilda wakes, she's in a bed at Bush Hill, a hospital staffed by Dr. Deveze and other French doctors who, unlike Dr. Benjamin Rush, don't believe in bleeding their patients. Instead, they recommend bed rest and food. Right on! Mrs. Flagg, a nurse, flirts with Grandfather and helps Matilda get back on her feet.
Once recovered, Matilda and Grandfather return to the city where they unfortunately find the coffeehouse completely ransacked by looters and thieves. Matilda does her best to provide food for herself and her grandfather, scavenging what she can from the small garden. One night, though, robbers enter the coffeehouse through an open window and attack Mattie, who's sleeping downstairs. Grandfather intervenes and gets injured in a scuffle with one of the robbers. He dies with Matilda at his side. It's all very, very sad, and Mattie, completely alone now, takes it pretty darn hard.
After seeing her grandfather properly buried, Matilda wanders around the city of Philadelphia. She finds an orphan in the doorway of a building named Nell, who has lost her mother. Taking Nell under her wing, Matilda soon tracks down a familiar face: Eliza, the former coffeehouse cook and one of Matilda's best friends.
Eliza takes Matilda and Nell to her brother Joseph's house, where Matilda meets Joseph, his twin boys, and Mother Smith, a crotchety old woman who's helping take care of the boys since their mother passed away. Matilda helps with the children and works with the Free African Society with Eliza, where they care for fever patients and their families.
Unfortunately, the children (Nell and the twins) soon come down with yellow fever themselves. Because Joseph's place is too hot, Eliza and Matilda move them to the coffeehouse, where they work day and night nursing the children. Eventually, the frost comes and the children's fever breaks. Matilda is reunited with hunky Nathaniel Benson in the marketplace. People from the country start filtering back into the city, including President Washington.
The coffeehouse opens back up and Matilda asks Eliza to be her business partner. After a little coaxing, she agrees. Nathaniel Benson starts coming around, and Matilda hangs his paintings on the walls of the coffeehouse. Eliza organizes a feast of thanksgiving for the whole clan: Mattie, Mother Smith, the twins, Joseph, and even Nathaniel.
Eventually, Matilda's mother returns to town, and the two are reunited. It's clear that Lucille is not as strong as she once was, but Matilda is building a new life, and a new family for them. With the memory of those they have lost, Matilda looks forward to the future of the coffeehouse and being with those she loves.