Yeto Vellipoyindhi Manasu story is about Varun (Nani) and Nitya (Samantha) are friends at an age of 8 and they stay in the same apartments. Then they join school together though their financial status keep growing apart. They study together in college. They have a typical on-and-off complex relationship. It could be ego, indecisiveness, stupidity or lack of long-term thinking. Whenever one person is fully committed, the other person goes on tentative mode. The rest of the story is all about how all ends well.