The main conflict in the novel comes from Margaret's need to settle her mixed religious heritage. She deals with her issues of belief in God, as the story is frequently interlaced with her praying by beginning with the title's words "Are You there, God? it's me, Margaret." In school, she is assigned a year-long independent study project; she chooses a study on people's beliefs, which proves to be more than she can handle as she is finding out a lot about herself as well. She also is dealing with conflict between her grandparents on both sides of her family, as her maternal grandparents are trying to guarantee that she is indeed Christian as she was born with a Christian mother. Margaret enjoys spending time with her paternal grandmother, who seems to accept her for who she is and is more accepting of her son's interfaith marriage, although she has referred to Margaret as "my Jewish girl" and introduced her to synagogue services for the purpose of showing her granddaughter what the Jewish faith entails, while her Christian grandparents claim her as a Christian. When her Jewish grandmother tells Margaret to remember that she's a Jewish girl, Margaret denies this and claims not to believe in God, which angers her grandmother. The ambiguities of her interfaith identity are particularly highlighted in a scene — following a heated argument with another girl — in which Margaret visits a church, finding her way to the confessional booth; there the unseen priest inquires as to her problems, but — believing at first that the priest is God Himself speaking to her and not comprehending the concept of Christian confession or its confidential nature — she simply responds "I am sorry," before running out of the church in tears.