In 2007, Melzer began the year with a first-round exit at the 2007 Qatar ExxonMobil Open and a semifinal exit at the 2007 Medibank International, withdrawing against James Blake. Melzer reached the second rounds of the 2007 Australian Open, the 2007 M.K. Championships, the 2007 Indian Wells Masters, and the 2007 Miami Masters. He also reached the final of the 2007 Tennis Channel Open, losing to Lleyton Hewitt. He also reached the quarterfinals of the 2007 U.S. Men's Clay Court Championships and the 2007 BMW Open. In the Masters Series on clay, he lost in the first rounds of the 2007 Monte Carlo Masters and the 2007 Rome Masters, and the third round of the 2007 Hamburg Masters, losing to Fernando González. After that, he suffered back-to-back losses to Juan Mónaco in the 2007 Hypo Group Tennis International and the 2007 French Open. He then suffered a left wrist injury in his first-round loss to Nikolay Davydenko in the 2007 Gerry Weber Open which caused him to miss two months of tennis, including Wimbledon. He came back at the 2007 Cincinnati Masters, reaching the third round and losing to Lleyton Hewitt. From then on, he was unable to secure back-to-back wins.