Both countries boast a maximum six points from their opening two matches, five points ahead of their four group rivals.
Portugal manager Paulo Bento said the result of this tie may determine his team's strategy for the remaining qualifiers, adding that he was setting his players the task of grabbing all three points.
"Our main goal is to earn automatic qualification for the World Cup," Bento said. "A win in Moscow will greatly boost our chances to clinch a direct pass to Brazil."
Bento also said that Russia's Italian manager Fabio Capello had added accuracy in their defensive play since he took over. "The Russian team have great attacking potential. The recent European championships proved it," Bento said.
"And they seriously boosted their defensive performance after they invited Capello to coach them. In the Moscow match we are set to play our regular attacking style football. But I'm afraid we will have to play in defence more than we want to."
Portugal are expected to field a full-strength squad as their star striker Cristiano Ronaldo's shoulder sprain, suffered in Real Madrid's 2-2 draw against Barcelona last weekend, was insignificant.
Arsenal forward Andrei Arshavin, Reading striker Pavel Pogrebnyak and former Tottenham attacker Roman Pavlyuchenko were all left out of his squad.
The 66-year-old coach continued his Russian rejuvenation, calling up 22-year-old rookie Maxim Grigoriev of Lokomotiv Moscow to boost his team's attacking line.
Capello has also summoned skipper Igor Denisov despite the 28-year-old midfielder's demotion from Zenit's first team into the youth squad after his revolt with the club chiefs over the salaries paid to big-money signings Hulk and Axel Witsel.
Denisov, lacking recent match practice, was following an individual training programme.
Russia are expecting a tough battle in what they have labelled the Group F decider.
"We will have to play against a very strong team, with a set of star players in its line-up," said Lokomotiv midfielder Denis Glushakov. "It will be a very uneasy match but our players are all in a brave mood after winning both of our qualifiers at the start."
Russia will likely enjoy strong home crowd support with a sell-out expected at the 85,000 Luzhniki arena with 63,000 tickets already sold by Wednesday.