The rappers appear together on new track 'Drop the World', and video director Chris Robinson has revealed he wanted to film the pair as if they were in an actual movie.
He said: "I almost take it like a feature film: How did Scorsese put Jack Nicholson and Leonardo DiCaprio in the same movie?
"You got two guys who are basically huge supernovas coming together
"As a director, it's how do you combine these two artists and create something that's special."
Although he wouldn't reveal the plot of the video, Chris maintained it will be different to most promos featuring two hip-hop stars.
Chris added to MTV: "When you have two artists together, it's like, 'Oh, they'll stand next to each other and that's it.' It's very awkward sometimes to have two very big stars.
"With this, it's kind of a surprise when Eminem comes through, and we matched it visually how Eminem enters the piece.
"From the concept and to just hearing the lyrics - with both of these amazing lyricists killing it - the whole video is just energy."
Lil Wayne is currently no stranger to video sets. He reportedly recorded nine promos in one day earlier this month, ahead of the start of a scheduled prison sentence on February 9.
Unlike the video for 'Drop the World', however, most of Lil Wayne's performances during his marathon video shoot were shot on Green Screen, so he could be superimposed when the rest of the footage is complete.
Wayne later escaped jail until March 2 after his lawyer argued he needed to complete dental treatment before starting his sentence.
'Drop the World' features on Wayne's album 'Rebirth'.