The plot follows the adventure of pagan farmer Piro which, annoyed and disgusted by Christianity, plans to kill Jesus Christ to prevent the rise of his religious phenomenon.

Grezzo 2 contains an equally exhaustive amount of NPCs pulled from various games and modifications, such as the innocent bystanders from Carmageddon and the Cabal cultists from Blood.

Occasionally, the player fights powerful "boss" enemies representing prominent figures of Christianity, such as Pope John Paul II, Jesus Christ, and God.

Piro massacres the event's reception, and dies shortly thereafter; he then falls into the afterlife to be judged by God, who is depicted as a short-tempered, foul-mouthed man adorned with cultist robes.

As a result of Grezzo 2's graphic violence, sexual content, and irreverence towards religious figures, the game received a significant amount of media attention.

[5][6] Kotaku editor Patricia Hernandez said that the content of the mod consists of killing several religious and other pop culture figures and that in the game, in her words, "nothing is sacred".

[8] Grezzo 2 received an honorary mention during the 2012 Cacowards, with the reviewer labeling the game as "the most psychotic thing to release this year", while praising the over-the-top presentation as "so bad it's awesome".

[9] After Grezzo 2, Giochi Penosi developed and released Super Botte & Bamba II Turbo, a 2D fighting game whose roster includes several characters of the Italian trash culture.