Steve Smith's return to Newlands after the ball-tampering scandal will officially go down as a "did not start".

His hoped of playing again in Cape Town have been abandoned twice now, first due to the COVID-19 pandemic that cancelled a tour five years ago; now wiped out by a neck complaint on Tuesday.

Smith's return to the venue where Australian cricket fell apart in 2018 before the then-captain received a 12-month ban in the aftermath was expected to be the story of the tour.

But as captain Pat Cummins put it on Monday, the cricket has largely done the talking over the past three weeks.

A come-from-behind win for Australia in Durban, and then one of a similar nature for South Africa, set up a compelling series finale in Cape Town.

And Australia would no doubt have liked Smith out there for it, even if the right-hander has endured a frustrating tour. 

Smith has made three scores in the 20s, suffered a heavy blow to the helmet in the first Test, then struggled with his neck in the second.

Australia had been very confident as recently as Monday morning that Smith would play, after he only batted for 20 minutes against gentle throwdowns in Sunday's main session.

But he grew increasingly uncomfortable in a 45-minute net session on Monday afternoon, then arrived before the team on Tuesday morning where his frustration grew.

And while Australia's medical staff tried to get the 37-year-old right, he ultimately felt he wasn't ready, and Josh Inglis was called into the team.

Just 18 hours earlier, Cummins had made clear how important it would be for Australia to have Smith on the field.

"He is huge, one of the greatest batters we have ever had," Cummins said then.

"You don't play 100-odd Test matches without playing Test matches where you're not 100 per cent fit.

"Even though he is probably not going to be 100 per cent hopefully he can compartmentalise that, like he has done a hundred times before with other things, and come out and contribute like he does every week."

Smith's absence means he will likely never play another Test in Cape Town, with Australia's away schedule beyond next year to be revealed in coming months.

Australia had been due to tour South Africa in 2021, before COVID initially prompted a bubble to be planned in Johannesburg and Pretoria, before the tour was instead called off.

Smith's injury will overshadow other major selection calls, with Australia's four changes the most mid-series since the events of Cape Town 2018.

Nic Maddinson and Beau Webster were dropped for Cameron Green and Cooper Connolly, while Nathan Lyon returned for Scott Boland.

Boland's omission will again create debate, with the unluckiest man in Australian cricket dropped after taking 5-81 in Gqeberha last week and standing up with the bat.

"You could consider him very unlucky," Cummins said at the toss.

"It's very hard, he's such a class player. As it was hard to leave out Nathan Lyon last week."