Nelson's last visit to the United States was a forgettable affair, an International Boxing Federation title defeat by James Warring in Fredriksberg, Virginia, in May 1992, when he lost on points.
He will fly out tomorrow to replace Joe Calzaghe as the British entry on the card of the Oscar De La Hoya against Felix Trinidad welterweight unification promotion at the Mandalay Bay Resort in Las Vegas on 18 September, with the chance to produce something special in the elite event.
The profile could hardly be higher for Nelson, who makes the third defence of his title against Tonga's Sione Asipeli only six weeks after his second- defence stoppage of Canada's Willard Lewis in Dagenham.
For a much-travelled fighter, who has ventured from Bangkok to Brazil and Copenhagen to Melbourne, Dagenham to Nevada must rate as the most bizarre and unlikely route of his career, but it could prove to be a significant journey.
The 32-year-old boxer said: "I've eliminated the negative aspects and that's been seen in England and Europe; now I've got to do it in America.
"Frank Warren, through his association with the American promoter Bob Arum, has done the business to get me this chance, it's now up to me to do the job in the ring.
"I've got to showcase myself and this is the time to do it, and hopefully I can go on an unify the title.
"This is a dream come true. It's like killing two birds with one stone - the whole world will be watching so there is a great opportunity for publicity.
"I've boxed all over the world and now that I am in my prime I want to show the best out there that I'm worthy of worldwide recognition.
"I can't wait to give Asipeli a roasting and show people that Johnny Nelson is ready to fight the best cruiser and heavyweights out there."
Asipeli, 25, moved to America after competing in the 1994 Commonwealth Games in Canada and has compiled a record of 15 wins, two draws and one loss, and that defeat has been avenged.
Asipeli, a former two-times Golden Gloves winner, is advised by the American manager Sterling McPherson, who handles the South African heavyweight Frans Botha.
In his only professional bout outside of the United States, Asipeli stopped the Welshman Tim Redman in Sheffield in two rounds on the undercard of Nelson's first-defence victory over Bruce Scott.
"I think Nelson and I will be closely matched," said Asipeli, who had a points win on the recent Botha-Shannon Briggs heavyweight bill in Atlantic City.