Ferguson said earlier this week that emulating the heroes of 1999 would be far harder than completing the initial historic hat-trick was 12 years ago.
Although there are some formidable barriers in the way, including a two-legged Champions League quarter-final with title rivals Chelsea and an eagerly-awaited FA Cup semi-final against neighbours Manchester City, Ferguson's assessment is more to do with the injuries he has to contend with.
Despite a two-week international break, Ferguson is actually worse off defensively than he was for the win over Bolton a fortnight ago.
Whilst the return of skipper Nemanja Vidic is a huge boost, the suspension of Jonny Evans and injury to Wes Brown deny him any selection options.
With Brazilian youngster Fabio virtually certain to slot in at right-back, United head to Upton Park weakened.
It is hardly ideal as the Red Devils visit a ground where they have triumphed on only six of their last 17 visits.
No wonder Ferguson is attaching such significance to the fixture.
"The big one is on Saturday because we are depleted in one area of the pitch," said the United boss.
"With eight games to go, you can't exclude anyone. Whoever is the most consistent will win this league.
"But we should not over-stretch ourselves in terms of looking forward. This game is as important as any."
Ferguson's point became obvious as he reeled off his massive list of injury problems.
On the basis that Jonny Evans will be available for Wednesday's Champions League trip to Stamford Bridge even if United resist the temptation to push Rio Ferdinand back into action two months after he was forced to pull out of the defeat at Wolves with a calf injury, Ferguson will have more bodies in midweek.
By the time his team square up to Fulham at Old Trafford on February 9, the United manager also expects to have Brown and John O'Shea in his squad, in addition to Ferdinand.
"I thought the two-week break would bring a few of them on," said Ferguson.
"It has but not enough for them to play on Saturday.
"We are considerably short for the right-back position. We have to solve that - and find the right solution."
If there is a silver lining this weekend, beyond the return to fitness of Anderson, who has been missing for five weeks with a knee injury, and Park Ji-sung, who has not featured since heading off to Qatar for Asian Cup duty with South Korea, it is that most of his players have been back at Carrington this week.
In part that is due to England boss Fabio Capello, who released Wayne Rooney, amongst others, after the win over Wales in Cardiff last weekend.
West Ham hope to have Scott Parker fit to face United.
The midfielder picked up shoulder and calf injuries on international duty with England and was left on the bench for the midweek draw with Ghana.
However, he is expected to pass a fitness test and rejoin a squad boosted by the return of Frederic Piquionne and Robbie Keane.
Manager Avram Grant believes West Ham have a bright future ahead of them if they can secure Premier League survival this season.
The Hammers endured a difficult start to the campaign as they battled with poor form and a plethora of injuries, but have responded well since the turn of the year.
The change in fortunes has helped propel the Londoners off the foot of the table and out of the relegation zone, although they still sit 17th in the table.
West Ham midfielder Mark Noble argued earlier this week that the squad's talent belies their lowly position and under Grant's tutorship they can reach the Champions League next season.
The former Chelsea and Portsmouth manager laughed off Noble's comments but admitted the future is rosy if they can stave off relegation.
"It is good that players have ambition but first we need to stay in the league," he said.
"As I said when I came here and even when we had difficult times, we have a vision at this club.
"Part of the vision is to be in the top third of the league and I think we can do it, but we need to do it step by step.
"First we need to stay in the league, second we need to analyse what we can do better in the next season.
"One thing I agree with Mark about - without mentioning the Champions League - is that this team is a good team and we can improve. In the next year we can get better and better."