Rose Lorkowski (AMY ADAMS) is a single mom who works as a maid to raise her 7-year-old son, Oscar (JASON SPEVACK), whose inattentiveness routinely gets him in trouble, including at school. When the boy's principal states Oscar must be medicated to stay in school, Rose pulls him out, asking her long-widowed dad, Joe (ALAN ARKIN), to watch his grandson.
Now in need of extra income for private school, Rose gets an idea from her married lover, local Albuquerque cop Mac (STEVE ZAHN), who states that there's money to be made in cleaning up the mess left after violent deaths and other bloody incidents. She ends up talking her younger adult sister, Norah (EMILY BLUNT), who still lives at home with their dad and can't even hold down a job as a waitress, to join her in the new business endeavor that they call "Sunshine Cleaning."
With supplies, not to mention business regulation advice from janitorial supply salesman Winston (CLIFTON COLLINS JR.), the two sisters set off doing their lucrative but gross work. During one such job, Norah finds an array of photos of Lynn Wiseman (MARY LYNN RAJSKUB), whose mother has recently committed suicide. When Lynn thinks Norah is following her, Norah can't admit why she's there, and the two end up becoming unlikely friends.
At the same time, Rose thinks she might finally be making it in life, but must contend with her affair with Mac as well as unexpected developments in both her personal and business matters.