Fredo had previously been hospitalized for liver and kidney problems due to drug addiction.
It progressed into the mainstream in 2012 when Fredo, along with other rappers and producers like his cousin Chief Keef, 22, and Lil Durk, 25, brought attention to it through their local fans and strong internet following.
His debut album, Trappin Ain't Dead Yet, featured guest appearances from Kendrick Lamar, PeeWee Longway and Chief Keef.
The late rapper, born Derrick Coleman, and Chief Keef came up in Chicago's hip-hop scene in the early 2010s and released almost 10 mixtapes.
Drake shared with his followers a pic featuring him and the late Fredo, captioning it: 'Rest in Peace Santana. At the time of his death, Santana was working on the follow-up to Walking Dead.
What makes this even sadder is the fact that Santana left behind an infant son, by the name of Legend.
Friends and associates took to Twitter to share their memories and condolences, including Drake, in whose 2013 video for "Hold On, We're Going Home" Santana appeared prominently.