Hyderabad Blues 2 picks up the thread at a point where six years on, Varun Naidu (Kukunoor) and his wife Ashwini (Jyoti Dogra) have settled into the monotony of marriage.
Friends Seema (Elahe Hiptoola) and Sanjeev Rao (Vikram Inamdar) have two children: Riya and Rahul. Looking at the happy family picture, Ashwini also wants children. But Varun is content with his life -- work, wife and friends -- and does not want to complicate it with children.
In keeping with Ashwini's dislike for the US, Varun has moved back from the US and has set up a call center in Hyderabad. Ashwini plans to set up her own clinic.
As the societal and parental pressure to have a baby increase, Varun and Ashwini turn to their friends, Sanjeev and Seema respectively, for advice. The girls get desperate enough to take Shashi Auntie into confidence.
Meanwhile, Varun demotes his call centre's floor supervisor, Azam (Anuj Gurwara), for sexual harassment. He appoints Menaka (Tisca Chopra), a Mumbai girl who has just moved to Hyderabad, in his place. Menaka embodies the bindaas attitude and makes no bones about the fact that she moves from job to job because she falls in love with her boss.
Varun and Menaka soon bridge the boundary between boss and employee and become friends. Not long after, Menaka begins the art of seduction. Will Varun resist? How will he and Ashwini deal with it?