After claiming a first win on South African soil since the sides first met in Balmoral Showgrounds in 1906, Joe Schmidt is hopeful of leading Ireland to a second success in two weeks and claim a historic Test series.
Their football counterparts will themselves be in unknown territory this weekend at the European Championships, and while the bookies don't believe either Irish team will make it one of the most successful weekends in our sporting history, try telling that to the respective camps.
The nation is busying itself for a nerve-jangling encounter with Euro 2016 hosts France for a place in the quarter-finals and coming the weekend after bitterly disappointing defeats by Belgium and South Africa respectively, another day of fingernail biting lies in wait.
Whatever about politics, a week really is a long time in sport.
If the home nation expects in France, that will be replicated in Port Elizabeth by Springboks eager to avoid what would be an embarrassment from their perspective.
Senior officials within South African rugby have publicly stated a series defeat would not reflect well on new head coach Allister Coetzee, who himself wasn’t overly impressed by Ireland in the defeat at Newlands.
“They weren't interested in playing,” he said in the aftermath of the 26-20 defeat.
“All they did was make it as difficult as possible for us to exit, just put it in behind us, turn us and we were actually bogged down in our own 22 there.”
Ireland have won just a quarter of their 24 Tests against the Springboks, but that ground-breaking win in the opening game of the series was made all the more unlikely by the dismissal of CJ Stander in the first-half.
Travelling with such a depleted squad – Schmidt was minus the services of Johnny Sexton, Luke Fitzgerald, Rob and Dave Kearney, Tommy Bowe, Josh van der Flier, Peter O'Mahony, Sean O'Brien and Simon Zebo – expectations outside the camp were low of upsetting the Boks.
The grit and determination shown down to 13-men at one stage in Cape Town and in the face of a second-half onslaught last week was there for all to see, while the skill and composure at key moments means the demanding South African public have every right to be nervous for the first-ever clash between the countries at the Nelson Mandela Bay Stadium.
Curiously, a couple of players who would have hoped to showcase their fine end-of-season form have struggled for game time.
Ultan Dillane has played for just 10 minutes and must make do with a place on the bench for the series finale, with Quinn Roux making his bow in last week’s 32-26 defeat.
That display yet again demonstrated his athletic ability with and without the ball, one particular tackle on midfield battering ram Damien de Allende, so influential a week later, adding credence to those who see the backrow as a more natural habitat for the 22-year-old.
Flying winger Matt Healy, the Guinness Pro12’s top-scorer, joins his provincial colleague among the replacements. A late call-up, many observers expressed delight at the prospect of the former Under-20 international in a different shade of green, but he awaits his first run-out.
Schmidt has reverted to experience for Saturday and the changes to the side hardly weaken prospects of a win.
CJ Stander, Keith Earls, Mike Ross, Luke Marshall, Jordi Murphy all return while Tiernan O’Halloran makes his first start after a three-minute cameo last time out.
Ross in particular will not lack motivation after losing his place to Tadhg Furlong. The young Leinster prop seemed entirely comfortable against a formidable pack at altitude, so much so that ‘The Beast’ Tendai Mtawarira was substituted with 20 minutes remaining at Ellis Park.
As Andrew Trimble mentioned earlier this week, the deflating nature of coughing up a 16-point lead as South Africa levelled matters in the series will have to be put to one side in order to succeed where no Irish team has previously.
Whether they do so will depend as much on the Springboks' attitude as their own.
Coetzee was so angered by their ill-discipline in their defeat at Newlands that he publicly revealed the harsh financial penalties for indiscretions on the pitch, but it appeared to make little difference a week later as Paddy Jackson profited from the tee in the early exchanges before the Boks went on the attack after the interval.
Repeat offending is likely to have the same consequence as Jackson grows more and more comfortable in the Test arena.
Can Ireland cope with huge physical threat of Ruan Combrinck and De Allende? Will Faf De Klerk show more of his club form after a tricky start to his international career?
Can the returning CJ Stander curb the influence of Francois Louw at the breakdown?
Will Eoin Reddan get the winning send off to his rugby career in a country so synonymous with defeat for Irish teams down through the years?
On a sporting weekend with so many possibilities, we won’t have long to wait for the answers.
