Vedam follows the intertwined fates of five individuals whose journeys collide on a single New Year’s Eve inside a hospital in Hyderabad. Vivek Chakravarthy [Manchu Manoj] is an aspiring rock star from Bengaluru and comes from a family of decorated army officers. His mother wants him to join the army, but he dreams of music. On the eve of his first major concert in Hyderabad, he misses his flight and travels with his band by road. A flat tire strands them, leaving him and Lasya alone. They are attacked by a fanatic group but manage to escape with the help of a truck driver. After a minor accident in Hyderabad, they rush a pregnant woman to the hospital.
Saroja [Anushka Shetty] is a prostitute from Amalapuram who longs to escape her abusive employer Rattamma. With her friend Karpooram [Nikki], a eunuch, she plans to flee to Hyderabad. After betraying the local sub-inspector Bullebbayi [Prudhviraj] by drugging him, she manages to escape, only to be betrayed again by a broker in the city. After a scuffle, Karpooram is stabbed, and the duo ends up at the same hospital as Vivek and Lasya, seeking medical help.
Ramulu [Nagayya] is a debt-ridden weaver from Sircilla, struggling to pay off a loan that has led to his grandson’s captivity. He and his daughter-in-law Padma [Saranya Ponvannan] are desperate to save the child and come to Hyderabad where Padma agrees to sell her kidney. Ramulu has already sold his own kidney in the past. At the same hospital, Padma’s kidney is sold for ₹1,00,000, though Ramulu only receives ₹37,000.
Rahimuddin Qureshi [Manoj Bajpayee], from Old Basti in Hyderabad, is deeply scarred by the miscarriage of his wife during a violent religious scuffle. He plans to leave the country, but on the night of his farewell, police arrest him and his nephews, alleging terrorist links. Rahim's nephew confesses to a terrorist connection, and Rahim is left trapped in the police station. While being transported to remand, Rahim tries to escape but is shot. He ends up at the hospital, alongside the other characters.
Anand Raj, known as Cable Raju [Allu Arjun], is a poor cable operator from the Jubilee Hills slum who dreams of impressing Pooja [Deeksha Seth], an upper-class girl who doesn’t know of his financial struggles. To gain entry into an expensive New Year’s party, Raju steals money by snatching chains from women. However, after a run-in with the police and a run-in with Saroja, Raju realizes his mistake when he steals money from Ramulu and later returns it, adding his own savings to make up for the theft.
At the hospital, the five lives collide when terrorists, holding Rahim hostage, free their leader. Vivek and Cable Raju try to save as many people as possible, even killing two terrorists in the process. Rahim, seeking redemption, saves his former enemy Shivaram [Ravi Prakash], and helps thwart the attack. In their final moments, Raju and Vivek heroically sacrifice themselves to protect the innocent.
In the aftermath, Saroja decides to leave her profession, and Vivek is posthumously hailed as a national hero. Raju’s death is mourned, but he earns respect, with Pooja visiting his grave. Rahim is freed by Shivaram, who recognizes his heroism. As for Ramulu, the landlord tries to deceive him about the money owed, but Ramulu’s grandson proves the payment is complete, and they are finally freed.
