Muscala played for the Bucknell Bison men's basketball team for four seasons. He was the 2011 Patriot League Men's Basketball Player of the Year after leading the Bison to an NCAA Tournament appearance. In addition, he was named to the First Team All-Patriot League and AP All-American Honorable Mention in 2010-2011. He was a 2012–13 Academic All-America selection. He was also a 2012–13 Senior CLASS Award finalist. Muscala also earned more hardware in 2013 as he won the 2013 Patriot League Player of the Year, Defensive Player of the Year, and First-Team All Conference honors. Muscala became the first player in Patriot League history to earn Player of Year and Tournament MVP twice. During his 2012–13 campaign, Muscala also become Bucknell's all-time leading scorer surpassing Al Leslie's 32 year record.
Muscala was selected with the 44th overall pick by the Dallas Mavericks in the 2013 NBA draft. He was then traded with 16th pick Lucas Nogueira and guard Jared Cunningham to the Atlanta Hawks for the No. 18 pick, Shane Larkin. On August 1, 2013, Muscala signed a one-year deal with Río Natura Monbús of the Liga ACB. While in Spain, Mike averaged 14.6 points and 7.8 rebounds per game in 20 games. He shot 54% from the field and 87% from the free throw line. On February 25, 2014, he left Spain to return to the United States. Two days later, he signed a multi-year deal with the Atlanta Hawks and made his NBA debut in a loss to the Phoenix Suns on March 2, 2014, where he recorded 4 points and 5 rebounds.