Because it does not have a typical narrative arc that follows one or a few main characters, Manhattan Transfer is full of conflicts and climaxes unique to each individual. These conflicts all have the city in common, and Dos Passos has set Manhattan up as the antagonist for all of his characters. The city is materialistic and judgmental, and even the wealthy characters feel the bite of Manhattan’s cold nature. As a result, the characters often resort to self-destructive choices to get by in New York. The montage style of the novel results in a book full of characters representing thousands of others like them. Set in the early 1900s, the city is undergoing profound changes. It is expanding as skyscrapers are becoming common, and relatively new infrastructure like the subway and elevated trains give the city a new frenetic energy. Manhattan Transfer is not so much about individual stories and a focus on deep character development, but rather the city’s effect on the human experience as reflected in the characters.  

The obsession with money and appearances that runs through the novel serves as a critique of twentieth-century capitalism in America. The promise of New York’s opportunities draws characters into the city, but they all suffer from the shallow standards that are the norm. The central conflict for Ellen, Jimmy, and Stan is that they seek success and happiness in a city that is constantly working against them. Ironically, while they have most opportunities in a wealth-obsessed New York, they are the ones most susceptible to making self-destructive choices. Ellen grows up in a home where she does not have an example of a healthy marriage, so she has a distorted notion of its purpose. Since she wants financial success, she uses marriage as a tool to obtain it. She misses her only opportunity for real happiness with Stan. When she has Stan’s baby, the child’s arrival does not figure prominently into Ellen’s unemotional world, other than it compels her to marry Jimmy so that the baby has a father. The climax of Ellen’s story comes when she finally decides to marry George Baldwin, who has pursued her throughout the novel. Again, she uses marriage to give herself a secure future. On paper, she will have achieved the monetary and social success that has always been important, but Ellen’s falling action finds her miserable because of her choices.  

Stan is the son of a wealthy lawyer who has been surrounded by money all his life and has never been held accountable for his actions. This sets him up for a life of aimlessness and hedonism. Unlike Ellen and Jimmy, he does not show interest in professional success. His conflict is that he looks for fleeting happiness and release from his demons. This leads to his excessive drinking and inability to build meaningful relationships. Even after falling in love with Ellen, he cannot help himself. Ellen and Jimmy, his closest companions, tell him he needs to stop drinking but do not help him in any meaningful way. Without having to face real consequences for his self-destructive behavior, Stan's climax comes when he drinks himself into oblivion and ends his life in a fire in his kitchen. He leaves behind a wasted potential and pregnant Ellen, who will never completely recover from his death.  

Sharing Stan’s lack of direction, Jimmy was born into a family that could have paved the way for a successful future, but he chose to become a reporter. At odds with the city since his mother died when he was young, Jimmy moves from job to job at New York newspapers. His conflict is his battle with the city as he tries to find success as a journalist. He is thwarted by his lack of passion and increasingly radical political ideas. He is happy for a time after he and Ellen marry in Europe during the war, but the relationship devolves when the two return to a materialistic city. The relentless focus on money and success in the city eats away at the couple. Jimmy does not make enough money, and Ellen has to work. The climax of Jimmy’s story comes when his marriage to a damaged Ellen falls apart, and he finally decides to leave the city for good. He is immediately lighter and feels a kind of hope that he has never had before. In the last pages of the book, Jimmy's resolution centers around his escape from the city on a foggy morning.  

The characters at the bottom of the financial ladder often have anarchist sympathies, longing for the day when the proletariat will take its place at the top of the city’s social structure and finally have access to the finer things they have been unjustly denied. Anna Cohen is a tragic example of how New York consumes the working class that will never achieve its lofty goals. Her vignettes show that she is repeatedly mistreated by employers, which Anna suspects is because she’s Jewish. Anna’s conflict is that she wants a simple happiness that the city will not allow her to achieve. After a series of bad experiences at work, she eventually takes a job at a seamstress shop, working as a scab during a garment workers’ strike. As her story reaches its climax, Anna is severely burned during a fire in the shop. As with many minor characters, her story is never definitively resolved, though it is implied that she will receive financial compensation for her injuries. Here, the city punishes her once again. Anna might end up with the money, but her life will be changed because of her disfiguring injuries. 

The novel retains its relevance a century later and in a completely different age, as Manhattan is still a metropolis where social status and wealth matter. The conflicts experienced by the characters are universal and relatable, whether they are immigrants arriving with nothing or wealthy, established professionals. In Dos Passos’s Manhattan, characters across the economic spectrum constantly talk about their unhappiness with the city’s blind obsession with success. New York City even assaults the characters in a physical way, as the elevated train rattles overhead, drowning out conversation, and grit is constantly blown in their faces. These assaults also have a universality, as the city does not discriminate when doling out its cruelty. Many characters talk about leaving, and while few of them put down roots holding them there, it is only Jimmy that takes steps to get out of the city for good. The other characters continue to get through each day as the city relentlessly moves around them.