A Secret Affair revolves on the lives of happy couple Rafi Delgado (Anne Curtis) and Anton (Derek Ramsay). On the eve of their wedding, Rafi backs out and seeks solitude in the US. Hurt and confused, Anton starts a physical relationship with Sam Montinola (Andi Eigenmann), one of Rafi's friends. Sam's obsession with Anton becomes a problem when Rafi returns and decides she wants to work things out with Anton.
Furniture supplier Ram (Derek Ramsay) is happily married to Charmaine (Cristine Reyes). One day, Ram lands a big client, a new luxury resort. But he needs the help of Kara (Anne Curtis), the daughter of the owner of the resort, to finalize the deal. Kara's help, however, comes with a price, because she fancies Ram to be her lover. Not before long, Kara successfully seduces Ram, even though she knows about his marriage. When Charmaine learns of the affair, she finds ways to fight for her husband's waning attention.
Amelia, a girl from a poor Ilocano family, decides to go abroad and find her fortune and also help her family. She becomes a maid of a royal family in the Middle East, which is running out of time, for the wife of the Sheikh is giving birth to a child. The newborn child is a son named Ahmed, and the Sheikh's wife asks Amelia to take care of the baby, to which she agrees. Amelia grows fond of the baby, teaching him to speak Tagalog and play tumbang preso.
Rica (Judy Ann Santos) has been very protective of her sister Cecil (Sarah Geronimo) even giving up her one true love Bong (JC de Vera) for her sisters future and after a freak accident 8 years ago at their little party store for fireworks, but as they grow up under the care of their grandmother (Gina Pareño) their parents come back (Tonton Gutierrez and Cherry Pie Picache). As they come back the girls are all grown up and Rica fears that her younger sister, Cecil, will no longer need her to look after her. Cecil later on meets and later falls in love with a con-man Edzel (Luis Manzano).
Ciara (Claudine Barretto) is a senior physical therapist who works for a rehabilitation center in the United States. She has devoted her entire life to her younger sister Julia (Anne Curtis) who was left in her care after the untimely demise of their parents.
Peter is a boy who is always maltreated by his father because of his homosexuality. He decided to run away and was found by a wealthy lady, Doña Biday, and is adopted by her. But he becomes abusive of his newfound wealth, and after the death of Doña Biday he becomes more abusive of his wealth and mistreated most of his housemaids, employees, and friends. Because of that, he was given a curse that transforms him into a horse every time he gets angry, or does/says anything bad to others.
They are everyday women who all live in a world where men rule business and women rule the office. In this comedy hit of the summer, the story begins with Paula, (Eugene Domingo) the daughter-in-law of Nimfa (Gina Pareno). She is the queen of fake designer bags. She gets high earnings from her living and uses them to put her children through private school, something that her irresponsible and unemployed husband cannot provide. Then there is a single mom, Ada (Jennylyn Mercado), a young woman who is a call center agent by night and a student by day, working hard to provide for her young son. In the process, she neglects her son and puts additional strain on her relationship with her mother, Sabel (Rio Locsin). Ada is also close friends with Tobz (Carlo Aquino) who is currently having issues with his girlfriend, Wendy (Cristine Reyes) also a busy woman who does not give him time nor pleasure and whose long life goal is to become an actress. While pursuing this, she meets Rodney (Rafael Rosell), who is also an attorney to celebrity plastic surgeon, Dr. Cleo Carillo. One of her clients/friends, Marilou (Ruffa Gutierrez), a beauty queen turned CEO upon the death of her husband, is also having problems with Amanda Dela Vega, her husband's daughter from another woman, and her own daughter, Dara Dela Vega (Bianca King). Dara is a Berkeley graduate who is eager to prove herself at her new job in a television show; she is struggling to manager her issues from home and her issues from her boss, Suzanne (Carmi Martin), Marilou's best friend. Another story follows Theresa (Iza Calzado), a nurse for Dr. Carillo's husband and who is content with her work but struggles to deal with her broken heart.
It has been six months since Laida Magtalas and Miggy Montenegro became a couple. Laida was promoted from executive assistant to executive accountant, while Miggy has been doing well as he is being mentored by his older brother Art Montenegro. Laida gets an offer from her aunt to work in Canada where she is being given a good recommendation.
Antonio (Kenji Garcia) is a curious fifteen-year-old boy who is beginning to come to terms with his own sexuality. Although his straight best friend, Mike (Jiro Manio), has been supportive of his coming out, his first sexual conquest has led to the destruction of his friendship with his other best buddy, Nathan (Ferdinand Zandro Salonga).
Laida Magtalas is a modern-day Belle. "Miggy" is the youngest member of the Montenegro clan – a well-established family in the business. She applies as an Editorial Assistant at Miggy's newly launched men’s magazine, "Bachelor". Laida revels working in such close proximity with the man of her dreams.
Four women named Res (Candy Pangilinan), Gay (Pokwang), Dolly (Eugene Domingo) and Brite (Ruffa Mae Quinto) who swore to be friends forever, become domestic helpers when they go over to another country. However, Res is beaten to death by her employers (Vice Ganda and Rychard Everly), making the other three worry because her husband gave her one condition if she comes with her friends: that she comes home safe, sound and alive. Brite, Gay and Dolly decide to bring their dead friend Res home.
Half-sisters Aileen (Judy Ann Santos) and Romina (Jolina Magdangal), along with first cousins Sandra (Iza Calzado) and Ruth (Rhian Ramos), reunite in Camiguin to bury their grandmother. Accompanied by Sandra’s friend, Lucy (Desiree Del Valle), the five girls dare to call on the spirits of the dead when they find their old Ouija board from when they were kids. The Ouija board is burned by accident before they are able to finish the ritual, trapping a murderous entity around them. As they begin to realize the terror that they have brought upon themselves, Aileen and Romina’s hostile relationship become even more strained, while Lucy’s sanity brings a heavy burden on Sandra, and Ruth’s boyfriend, Gino (JC De Vera), is unknowingly pulled into the danger and horror that await all of them.