The Belgian rider, who celebrated his 31st birthday last Sunday by winning the world road race title in Lugano, needs a strong placing in the 250-km classic to make sure of the honour in the penultimate event of the series.
He leads the standings on 162 points, with Italians Andrea Ferrigato and Michele Bartoli, the bronze medallist in Lugano, still in contention on 126 and 124 points respectively.
Both men will be doing all they can to thwart Museeuw's march towards the crown but the Belgian can count on his Mapei-GB team mates to try to shut them out at the finish in what promises to be a highly tactical race to Bergamo.
``We will all be riding for Museeuw to help him win the World Cup,'' said Andrea Tafi, who was second in Thursday's Tour of Piedmont.
``I could win the Lombardy myself but what counts is making sure Ferrigato and, above all, Bartoli don't get any points.''
Saturday's race will take riders through four steep climbs in rapid succession, with the field facing a slog to the 763-metre Colle del Gallo just 30 kms from the line.
Museeuw, winner of April's Paris-Roubaix, won the World Cup crown in Bergamo last year despite failing to finish.
He skipped the Tour of Piedmont and was never in contention in last Wednesday's Milan-Turin race, blaming the after-affects of his victory celebrations in Lugano.
``My head was not there,'' Museeuw said in Turin. ``I obviously haven't recovered after winning the gold.''
Frenchman Richard Virenque, winner in the Tour of Piedmont, is out of contention for the World Cup crown but is still hoping to scotch Museeuw's title ambitions after losing out in Lugano.
``The Tour of Piedmont was a dress rehearsal for the Tour of Lombardy. That will be the real re-match after the world championship,'' he said.
Saturday's winner will reap 50 points, with 35 for second and 25 for third. The final race of the 11-event series, the Japan Cup, is on October 27.
Tomorrow, the Lombardia will be raced for a second time from Varese to Bergamo. In 1994, the finish was in Monza. In 1995, on the new route, Gianni Faresin won in Bergamo ahead of Daniele Nardello and Michele Bartoli.
Lombardia is the penultimate race of eleven World Cup races for 1996, which is lead by Belgian Johan Museeuw. The eleventh race will be held on Sunday 27, when the Japan Cup will be raced in Japan.
Only one rider has won five time at Lombardia: Fausto Coppi, consecutive winner from 1946 to '49 and then in 1954. Alfredo Binda won four: 1925-'27 and 1931. Bartali, Belloni and Girardengo won three.