De Minaur battled back from going one set down to force a decider where he held a 5-3 lead, only for Musetti to win four games in succession in an incredible round-robin match in Turin that the Italian won 7-5 3-6 7-5.
"I think it's probably a good thing I don't express my feelings right now because they're quite dark," De Minaur said.
"It just feels like it's been that type of year where I've had what feels like a whole lot of matches that should have gone my way and just somehow don't."
At the U.S. Open in September De Minaur won the first set against Felix Auger-Aliassime but ended up losing his sixth Grand Slam quarter-final. At Wimbledon in the fourth round, he won the opening set 6-1 against Novak Djokovic only to suffer a similar fate.
"It's something that if it doesn't get sorted, it's going to eat me alive," the Australian said.
"I need to get it sorted sooner rather than later. I don't know how many times I can deal with a loss like this one."
De Minaur lost his opening Jimmy Connors Group match against world number one Carlos Alcaraz on Sunday, and takes on last year's losing finalist Taylor Fritz in his final round-robin match on Thursday, where defeat would end his time in Turin.
The Australian was asked what else he can do to avoid another crushing loss.
"Just have a talk to my team and try to sort out these issues because these are issues that can't keep happening," De Minaur replied.
"I mean, if I really want to be serious about taking the next step in my career, these matches, I can't lose them. I just can't."