It could be a new dark wizard that we haven't seen in the original series. This wizard might be jealous of Harry's fame and power and wants to eliminate him by making him disappear.
One possible plot could be that Harry has been kidnapped by a dark wizard who wants to use his powers for evil. Another could be that he has run away to find a way to defeat Voldemort on his own without endangering his friends. Maybe he's lost in a mysterious magical realm while on a quest and can't find his way back.
Voldemort's remaining followers could be suspects. Even though Voldemort is gone, there might be some die - hard supporters who still hold a grudge against Harry. They might have kidnapped him to try and revive the dark side. Another suspect could be some jealous wizard who has an eye on Harry's wife. He might think that with Harry out of the picture, he can get closer to her.
It could be that there's a magical curse that causes him to vanish. His wife, being a strong - willed character, decides to study all she can about the curse. She teams up with some powerful wizards and witches in the wizarding community. As she delves deeper into the mystery, she uncovers secrets about Harry's family that she never knew before, which may be the key to finding him.
The Hogwarts letter could act as a tracker. Since it's magically bound to Harry, it might start to glow or move in a certain direction leading to where he is. For example, if he's been taken to a secret lair, the letter could lead his friends right to the entrance.
The Hogwarts letter might be the key to understanding Harry's disappearance. Since it's a connection to the wizarding world, it could be that there are hidden messages in it that only become visible when Harry is in trouble. The Ministry of Magic could get involved as well. They might suspect that Harry has run away deliberately to avoid some new danger that they are not aware of, but the letter could prove otherwise and lead to a race against time to find him before it's too late.
His friends would be extremely worried. Hermione would immediately start researching every possible spell or charm that could be used to find him. She might also look into any historical records of similar disappearances during Auror missions.
It could be Orochimaru. He's always been interested in Naruto's power, especially the Nine - Tails within him. He might have come up with a new devious plan to capture Naruto and use his power for his own dark experiments.