The death of parents
The memoir opens with the recounting of the Eggers children trying to convince their mother to fight for life. Then, we learn in a flashback that Eggers also suffered the loss of his father, but he left the funeral to have sex with his girlfriend. That juxtaposes the idea of sexuality, union, and new life with the idea of death, removal, and tragedy. All these symbols point the reader to the sublime strangeness of existence. The plot of human life is exotic and confusing, even though it is primary and obvious.
MTV
When Eggers misses his opportunity to get famous on MTV, that is a clearly symbolic moment in his life. It shows through tragedy and failure what he wants most in life. He feels his life is so beautiful and worthy of attention that he is thrilled by the idea of celebrity. He feels he is a suitable object of worship and public attention, but he fails. This symbol points to his fame as a writer, so that the reader can see that his fame is the fulfillment of a deep existential longing for his life to matter in a public way.
Suicide and depression
When John commits suicide by overdose, Eggers inherits John's depression during a season where Eggers himself was dealing with extreme depression, frustration, and loneliness. This leads to a sublime moment of clarity where he must either pick life or death. The depression is compounded even more by physical agony when he has to pass a kidney stone—one of earth's most painful ailments imaginable. He is a full-blown witness of suffering, which leads to existential dilemma: what is all his suffering worth?
Closure and acceptance
The final act of the memoir shows Eggers accepting the ashes of his parents, ending his popular magazine, and moving with Toph to New York. Without context, perhaps these decisions would be happenstance, but in light of Eggers suffering, the decision signifies a newfound acceptance of responsibility. He knows the truth about life and its agony, and he is deliberately choosing to continue in his journey. The Heartbreaking Work of Staggering Genius is the story of his awakening—not a story that he authored, but a story that literally authored him.