Milo will follow his This Is Us co-star Sterling K. Brown into the Amazon Prime series, as the Black Panther star appeared as Reggie in season 3.
Milo's casting follows Sherman-Palladino previously teasing that Ventimiglia's involvement would "definitely happen."
"Don't think it has not been discussed!" She told Variety.
"It's got to be the right part. It can't be just a cameo. It's got to have some meat to it. And it's also got to be a time when he can shave and cut his hair into a 1950s-period look. But the reuniting will definitely happen."
Speaking previously to Digital Spy, This Is Us executive producer Elizabeth Berger said: "We've been doing it for a long time, and many of us have been there from the very beginning, and have moved through the years together.
"We love the show, and it will be a big, emotional deal when it comes to the end."
This Is Us is shown on NBC in the US and on Amazon Prime Video in the UK.
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