"Una Maid in Manhattan" tells the story of Marisa Lujan (Litzy), who runs a small hotel in a village in Michoacan. Before the events shown in the show, she falls in love with Victor, an American man who visits Michoacán every year for the Christmas holidays. She becomes pregnant with Victor's child.

At the start of the show, Marisa's son, Lalo, is ten years old and Marisa's dream of a happy life with Victor has given way to a more troubling reality: the town has become a center for drug trafficking. Among the seedy inhabitants is Miguelito, an old friend of Marisa's who now heads a powerful cartel which buys Marisa's hotel and turns it into a headquarters for drug deals and murder.

Marisa decides to migrate north to the United States for the sake of her son. Victor proposes to her and thus provides means of obtaining legal documents to live and work within the United States. In Los Angeles, Marisa and Victor are married, but things quickly sour when Marisa catches Victor cheating with another woman on their wedding day. She quickly decides to move to New York, where her childhood friend Belinda (Maite Embil) offers help. Thanks to Belinda's good word, Marisa finds employment as a maid in a Manhattan hotel and, through good work, begins to gain the trust and respect of the hotel manager. Consecutive wins as Employee of the Month and the encouragement of her maid friends begin to convince her that she should apply for the open position of assistant manager.

Her aspirations for advancement are complicated by a mixup involving Cristobal Parker (Eugenio Siller) a wealthy man and New York Senator's son, who is staying at the hotel. Cristobal Parker follows Lalo into the premier suite only to find Marisa dressed in a rich guest's glamorous clothes. After a walk in Central Park, he begins to fall in love with Marisa. She, in turn, feels for him what she had convinced herself was not possible after her problems with Victor and other men.

However, Marisa is also a responsible and loving mother and woman. Although she admits to very much liking Cristobal, she cannot justify jeopardizing her son's education or her job for what she considers to be a fairytale. Also in the mix is Sara (Vanessa Villela), another hotel guest and a vapid fashion critic who has set her sight on Cristobal Parker.

Though Cristobal is smitten, Marisa feels guilty about misleading him about her true identity as a maid. She is also reluctant to continue seeing him as she is worried about the status of her job and as she considers they come from far too different backgrounds to make things work. It will take both characters' willingness to see things from a new different perspective and a willingness to turn things upside down to make things work.