Following the release of three studio albums as part of the group Organized Konfusion, Prince Po focused on his solo career.

[3] By 2014, he had released numerous projects, both solo and as part of the Gangrene duo with the Alchemist,[4] and had composed several soundtracks, including the soundtrack for 2013 video game Grand Theft Auto V.[5] Prince Po and Oh No met when Prince Po was working on Madlib-produced Percee P's album Perseverance (2007).

Immediately, the two started working together, with Oh No sending beats and Prince Po presenting his unfinished verses over the phone.

[13] HipHopDX's Jay Balfour also thought the album "does end up striking the same note at least one times too many", but still viewed it as a "thematically aggressive project" that isn't overly simplistic.

The reviewer asserted that Animal Serum lacks the level of excitement of Oh No's previous albums and that Prince Po's "flaky metaphorical framework frequently falls short", listing "Machine Rages", "Toxic", and "U" as highlights of the record.