American Mayweather has regularly flirted with the idea of competing in an MMA bout, with a series of recent posts on social media seemingly calling out Irishman Conor McGregor.
The 40-year-old beat McGregor in a boxing match last August with Ultimate Fighting Championship president Dana White claiming a rematch will only happen under MMA rules.
Pacquiao has leaned away from confirming any desire to complete the crossover however remains interested in the sport having bought shares in ONE Championship, Asia's leading MMA organisation.
The Filipino also claimed to have been in talks to fight McGregor last year, in the event the UFC superstar's negotiations with Mayweather collapsed.
Briton Khan, who has indicated a willingness to make the move to MMA himself, believes neither fighter will ever make the switch due to the technical differences between both sports.
"I don't think they [Floyd Mayweather or Manny Pacquiao] will ever step in the cage," Khan, who will make his boxing comeback in May against Phil Lo Greco, told Sky Sports, via Twitter.
"MMA is a very difficult sport, you need to have a lot of strength and takedowns and I just don't think a boxer is just gonna have all the tools to fight someone in an MMA cage, it's gonna be really difficult.
"I've been seeing Mayweather talking about and taking a lot of videos and pictures inside the MMA cage, but I just can't see that ever happening. I can't see him ever stepping in with someone in the MMA cage."
Speculation that Mayweather could indeed step into the Octagon has intensified in recent weeks, with the 50-0 boxing legend posting a series of images on his Instagram account, including one photoshopped picture of him fighting McGregor.
In January, he released footage of him training inside an MMA ring, though it remains to be seen whether he will substantiate these teasing posts with a genuine desire to switch sports.
However, the five-weight world boxing champion has stated his desire to fight again despite refusing to confirm in which code his next appearance will occur.
"Will you guys ever see me in a boxing ring again? I don't know," he told Forbes. "We don't know if it is a boxing ring, or maybe an octagon. There have been talks about another multi-billion dollar deal. We will just see."