Melton and teammate and center Roberto Garza were eventually named to the USA Today All-Joe Team. In 2012, during organized team activities (OTAs), Melton appeared in the backfield as a running back, resembling former Bears defensive lineman and fullback William Perry; Melton had not played running back since his days at Texas. In the season opener against the Indianapolis Colts, Melton sacked Andrew Luck twice as the Bears went on to win 41–21. On December 26, Melton was named to his first Pro Bowl. In the 2012 season, Melton recorded 32 tackles and six sacks, tied for third in the league among defensive tackles. On March 1, 2013, Melton was given the franchise tag by the Bears, worth $8.45 million. In 2013, Melton was carted from the field during the third game on September 22, against the Pittsburgh Steelers, with a left knee injury. A Lachman test on the field was indicative of an anterior cruciate ligament injury, and an MRI was scheduled. On September 23, Melton was ruled out for the remainder of the 2013 season, and was placed on injured reserve four days later. On March 18, 2014, Melton signed a 1-year contract along with incentives, including a team option for 3 more years with the Dallas Cowboys, hoping he could regain his Pro Bowl form. After missing the last 13 games of the 2013 season with a torn ACL, he struggled in training camp as his knee recovered and he worked through a groin strain. Although he began the season as a starter at defensive tackle, injuries forced him into a pass-rushing role, with Tyrone Crawford passing him on the depth chart. His production faded as the year went on and his season ended with a bone bruise on his right knee and being placed on the injured reserve list before the playoffs. He finished with 5 sacks (registered in the first 9 games), 20 tackles, 17 quarterback pressures, 4 passes defensed and 2 fumble recoveries. On February 14, 2015, the Cowboys declined to exercise the contract's three year option, allowing him to become a free agent on March 14, 2015. On March 12, 2015, Melton agreed to terms and signed a one-year contract with the Tampa Bay Buccaneers, reuniting him with his old head coach Lovie Smith. He was a backup that was used at defensive tackle and defensive end, posting 30 tackles (second highest mark in his career), 2 sacks, 2 passes defensed and 2 fumble recoveries. On August 21, 2016, Melton signed a one-year deal with the Denver Broncos.