[2] Twenty years after the events in the first Django, the eponymous deadly gunslinger has left his violent life behind and become a monk named Brother Ignatius.

Suddenly, he learns from a dying former lover that some time ago he had a young daughter, who has been kidnapped along with other children who are now working for a ruthless Hungarian criminal and aristocrat known as El Diablo (The Devil) Orlowsky, who commands a mercenary army and has made himself infamous as an arms dealer and slave trader.

Django Strikes Again was conceived concurrently with Duccio Tessari's Tex and the Lord of the Deep; both projects were intended to represent a revival of the Spaghetti Western genre.

Following the commercial failure of Tex, Sergio Corbucci, who had co-written Django Strikes Again and had initially agreed to direct it, refused to partake in its production.

[4] Following a 2014 attempt to mount the project,[5] it was reported in May 2016 that Franco Nero would reprise his role in a third and final outing as the titular character, entitled Django Lives!