He was rated as a five-star recruit and committed to Clemson University to play college football under head coach Dabo Swinney.

As a true freshman in 2015, he played in 13 games, recording 34 receptions for 582 yards and five touchdowns.

[4][5] He did not play in the 2015 Orange Bowl or 2016 College Football Playoff National Championship due to suspension for failing a drug test.

[6] Cain returned from the suspension in 2016, and played in all 15 games, including Clemson's 2017 College Football Playoff National Championship victory over Alabama.

[9] After his junior season, Cain decided to forgo his senior year and declare for the 2018 NFL draft.

[13] In the first preseason game, Cain suffered a torn ACL after a promising training camp, prematurely ending his rookie season.

[15] He made his NFL debut in the Colts' 2019 season opener against the Los Angeles Chargers.

[31] On March 8, 2023, Cain signed with the Birmingham Stallions of the United States Football League (USFL).

[35] He was released on August 27, 2023, as part of final roster cuts before the start of the 2023 season.