South Africa and Uruguay can seize control of Group A and take a huge step towards qualifying with victory in Pretoria on Wednesday.
Both sides opened their World Cup campaign with draws on Friday leaving the group finely balanced after one match with each team on a point apiece.
A win would change the dynamics of the group massively and pile the pressure on France and Mexico, who collide a day later in Polokwane.
South Africa will have been happier following their curtain raiser after coming within 11 minutes of victory in their 1-1 stalemate against Mexico.
The result came as a surprise to many, with the hosts given little chance of being in contention to make the knockout phase.
Uruguay also came out happier of Friday's fixture in their dour 0-0 draw against France, although their efforts were even more commendable given Nicolas Lodeiro's sending off left them facing a Les Bleus onslaught for the final ten minutes in Cape Town.
Coach Carlos Alberto Parreira could tinker with his back line for his team's second encounter.
Bafana Bafana let their advantage slip against Mexico after Siphiwe Tshabalala had put them in front 55 minutes in with the classiest of finishes and Parrerira will have been concerned by the uncertainty of his defence.
Rafael Marquez levelled late on to hand Mexico a point and defender Lucas Thwala could drop out of the starting line-up.
Thwala was replaced in the second period by experienced left back Tsepo Masilela and he could be handed a start in the only anticipated change for the hosts.
Star midfielder Steven Pienaar is also expected to continue despite recent complaints of fatigue following a demanding season at domestic club Everton.
Lodeiro will be the obvious omission for Uruguay following his dismissal late on in the France encounter.
The midfielder only entered the fray 63 minutes into the clash as a substitute but promptly picked up two yellow cards, the second of which for a crude challenge on Bacary Sagna.
Coach Oscar Tabarez is believed to be considering a change of approach to the one offered in their opening game, which offered little in the way of chances.
The Uruguayan chief could opt for three strikers in a more attacking mindset, with Diego Forlan expected to drop deeper and play behind Luis Suarez and Edison Cavani.