The MGM Grand in Sin City holds some happy memories for the Filipino welterweight, but it is also the scene of two of his biggest setbacks in the ring.
A controversial points loss against Tim Bradley in June 2012 was followed by a devastating sixth-round knockout defeat against Juan Manuel Marquez in the fourth fight of their epic rivalry six months later.
An overhand right from Marquez sent Pacquiao crashing to the canvas face first, where the first and only eight-division world champion lay unconscious for a few worrying moments.
"I saw the replay and it just happened. That's boxing. Sometimes you win and sometimes you lose. I am not going to complain or worry about what happened," said Pacquiao.
Many thought it was the time for Pacquiao, who has won world titles from flyweight all the way up to light-middleweight, to bring down the curtain on a glittering career and complete his transition into politics, where he is a congressman in his native Philippines.
The 34-year-old, however, begged to differ and is planning on resurrecting his career on November 23 in Macau, China against the tough but limited Brandon Rios.
Another defeat could be the the final nail in the coffin for Pacquiao (54-5-2, 38 KOs), who is in optimistic mood.
"The year off has been good and I am very excited to get back into the ring and fight and to do it for the fans. I feel very fresh, strong and fast," he said.
"I have been training very hard for this fight and right now I feel like I am 25 years old and training that way. I feel very good.
"My stamina and my quickness and power are there and I am very excited about that.
"I will not go for the knockout in this fight but if I have a chance to finish early, why not? But I am not thinking that I need to knock him out. In training if I focus on a knockout I will get careless in the ring on the night of the fight.
"So what I need to do is focus in training so I am ready to get in the ring on the night of the fight."
Rios' power will give Pacquiao's followers cause for concern following the Marquez bout, but the American's flaws were there for all to see after splitting a pair of decisions with Mike Alvarado.
Rios (31-1-1, 22 KOs), who built his reputation at lightweight, has also never fought in the 147lb division and his come-forward style of fighting makes him tailor-made for Pacquiao, who is understandably delighted with his next opponent.
"That's what I want - his style of fighting. He likes to come inside and I like that style. I don't like to chase and I'm pretty sure I won't have to chase him," he said.
Rios' trainer Robert Garcia has started the mind games by claiming Pacquiao is not the intimidating force he was a couple of years ago.
Pacquiao has never been one to get drawn into a war of words, though, and responded: "He tries to say the words that he thinks will anger me but they don't mean much to me.
"What I have to do is to prove it to them on the night of the fight on November 23. I can say the words too, but I have to prove it when we get in the ring."
Pacquiao is favourite to come out on top, and boxing needs him to.
After all, he has proven in the past that he is the only man that can give Floyd Mayweather a run in generating revenue, while his decision to choose China as the venue for his next fight could develop interest in one of the biggest untapped markets for boxing in the world.
Victory and an impressive outing opens up a host of possibilities, including a lucrative fifth showdown with Marquez.
Ever the humble professional, Pacquiao insists he is not looking past Rios.
"Right now I am not thinking about the next fight. What I have right now is focus on my training and preparation for Rios so I can be sure that victory is mine," he added.