Song was featured in a 2010 advertisement called "Sock Puppets" introducing the newly redesigned Kia Sorento SUV. It has also been used in the 2011 action adventure racing game Driver: San Francisco, in the closing credits for the 2012 role-playing first-person shooter Borderlands 2 and 2013 platform game Knack on the PlayStation 4, and in a TV spot for the 2013 animated movie Turbo. It was also featured in the ski film Attack of La Niña. In 2014 the song was featured on the in-game soundtrack of the racing game Forza Horizon 2 for the Xbox One and Xbox 360 on the fictional radio station Ninja Tune Radio and the official trailer of the comedy series Girl Meets World on Disney Channel in Southeast Asia. It also appeared in the multi-platform racing game The Crew on the fictional radio station 11 FM.
A remix of the song features in the video game LittleBigPlanet 3 while the original version appears near the end of the level "High Stakes Heist".
The song was also used as the theme song for Intentional Talk on MLB Network from the show's April 4, 2011 debut to April 1, 2016. A variant of this song called "How Do You Like Me Now (Beats Mix)" was performed by The Heavy and was prominently featured in the 2010 installment of Sony's venerable baseball video game franchise MLB The Show.
Beginning in the 2015-16 NHL season, the Vancouver Canucks play "How You Like Me Now" during home games at Rogers Arena whenever Radim Vrbata scores a goal, as part of their usage of personalized goal songs for each player. "How You Like Me Now" was selected for Vrbata's goal song in a fan vote.