New-look Italy's hopes of making an impact against a youth-filled All Blacks side were kept in check by a 10-tries-to-one rout in Rome last weekend.
But Irishman O'Shea refused to berate his players after the heavy defeat and insisted his long-term plan will see the misfiring Azzurri back to winning ways.
Italy have played South Africa 12 times and lost on each occasion, but this is a Springboks team on a wretched run.
Hooker Leonardo Ghiraldini and prop Andrea Lovotti both suffered injury in Rome and have been replaced by Treviso's Ornel Gega and Calvisano's Sami Panico respectively for Saturday's clash in Florence.
Giovanbattista Venditti has been called into the squad to replace Angelo Esposito on the left wing while Francesco Minto comes off the bench to replace Maxime Mbanda in the third row.
South Africa coach Allister Coetzee is under pressure following a poor run of results, including a record 57-15 defeat by New Zealand last month, and the 'Boks suffered their first defeat to England in a decade last weekend at Twickenham.
O'Shea, who signed a four-year contract in the summer, said after last week's test: “I have huge confidence in the squad... so long as we maintain our level of work rate and willingness to stick to a plan for 80 minutes, we can make a huge difference.
“I'm looking forward to playing South Africa next week. For me, the glass is always half-full.
“If we stick to our plan, the results will follow. If we don't, they won't.”
Italy have yet to announce their replacements.
The 'Boks will name their starting XV on Thursday.
Italy team to play South Africa at the Stadio Artemio Franchi in Florence on Saturday:
Edoardo Padovani; Giulio Bisegni, Tommaso Benvenuti, Luke McLean, Giovanbattista Venditti, Carlo Canna, Giorgio Bronzini; Sergio Parisse (capt.), Simone Favaro, Francesco Minto; Andries Van Schalkwyk, Marco Fuser; Lorenzo Cittadini, Ornel Gega, Sami Panico
Original source: Italy make four changes for South Africa clash