With one year remaining on his contract at the club, this season could offer Neville the opportunity to add to his collection for the final time.
Related ArticlesFerguson: Pain of Rome lingersMan Utd v Birmingham previewCentral role can retain titleFerguson: United are readyKey dates for 2009/10 seasonEurope's Premier power centreBut Ronaldo's £80m transfer to Real Madrid earlier this summer has left United without a player who scored a staggering 68 goals during his last two seasons at the club.
Summer signings Michael Owen and Antonio Valencia will be expected to make up some of the shortfall, but Neville is confident that the Ronaldo gap can be plugged.
And the 34-year-old insists that United can once again overcome the departure of a great player by delivering silverware.
Neville said: "We've seen great players leave the club before and coped. I played with Roy Keane for more than 10 years and I never thought we'd replace him.
"We never will, just like we won't replace Ronaldo like for like, but we can adapt. Roy left, Peter Schmeichel left, Eric Cantona left, but the club has remained successful.
"Look at how Michael Carrick and Darren Fletcher have performed in the last two years and you have to say we've survived Keane's exit.
"We'll do the same with Ronaldo. Losing somebody who scores that many goals is always going to be a blow, but there is more than one way to skin a cat.
"Nani and Ji-Sung Park will try to make that position their own, while the goals issue isn't a problem.
"Michael Owen has joined us and you might find Wayne Rooney flourishing. Dimitar Berbatov can bang them in as well."
A fourth successive title would leave United as the most successful club in the history of the English league championship, with a nineteenth success allowing them to move one ahead of Liverpool's tally of eighteen.
Neville said: "We always want to win the league. Reaching 19 isn't something we're talking about, although it will be brilliant if we do it.
"It's going to be incredibly difficult though. Nobody has ever won four in a row, which is a massive incentive. But we can't think too much about records."