The actual death occurs in the context of helping his brother Sasuke and playing a crucial role in the series' progression.

After breaking free from Kabuto’s control using Shisui Uchiha’s Kotoamatsukami , Itachi teams up with Sasuke to defeat Kabuto and force him to release the reanimation jutsu. In , as the jutsu undoes itself, Itachi’s soul begins to fade. Before departing for the Pure Land, he uses his Sharingan to show Sasuke the full truth of the Uchiha Massacre. He leaves Sasuke with the iconic final words: "You don’t ever have to forgive me... no matter what you do from here on out, I will love you always" .

In summary, Itachi Uchiha's death occurs in , a pivotal episode that explores themes of family, friendship, and sacrifice, leaving a lasting impact on the series and its characters.

Itachi Uchiha dies once in the canonical storyline (his death is not a recurring event; the phrase “die again” likely refers to a rewatch or reminder). His death occurs during the Sasuke vs. Itachi arc.