Cleary headlined a raft of big-name NRL halves returning from injury in Tuesday's team lists with Canberra's Jamal Fogarty also coming back, against the Warriors.
Adam Reynolds is also considered an outside chance of playing for Brisbane against Newcastle, in his first NRL match since rupturing his bicep in May.
But it is Cleary's comeback that has the potential to catapult the Panthers' push for a fourth-straight premiership.
Cleary ordinarily does the bulk of the kicking for Penrith in general play, but in his absence Jarome Luai has stepped up in recent weeks.
And coach Ivan Cleary said one thing being looked at by Penrith's staff was managing his son's workload.
"We've left no stone unturned. We've changed a few things, but haven't thrown out anything either," coach Ivan Cleary said.
"Definitely around some kicking loads. Other than that, he's just been doing some stuff behind the scenes strengthening it.
"He understood from when he did it, he wanted to make sure he wanted to tick every box on the way back.
"Now he's done that, he's pretty hungry."
The Panthers on Tuesday opted to rest NSW State of Origin duo Isaah Yeo and Dylan Edwards from the clash with the Dolphins, while Jarome Luai, Liam Martin and Brian To'o are all on an extended bench.
Ivan made clear there was no pressure on Nathan to come in and lift the Panthers, after being limited to just five games this year.
"I have to try and keep him understanding he will have to work his way back in," Ivan said.
"We can't just expect him to come back and do everything. In the past he has come back from injury strongly, so hoping that is the case.
"He's looked really good. It's been a while. We've probably been a little conservative."
Elsewhere, Fogarty's return from a bicep rupture could not come soon enough for Canberra, who have lost their last four to slip to 11th on the ladder.
Hudson Young will also return from a groin injury for the Raiders against a Warriors side who learned this week Tohu Harris (wrist) will miss the rest of the season.
The Warriors have also lost fullback Charnze Nicoll-Klokstad (calf) and Marcelo Montoya (groin) for the match, with Taine Tuaupiki to wear No.1 and Roger Tuivasa-Sheck to play wing.
Reynolds' return to Brisbane's team list, meanwhile, comes in the No.24 jersey with the halfback completing his first full training session on Tuesday.
The desperately out-of-sorts Broncos will wait until later in the week to decide if he, Pat Carrigan, Payne Haas, Reece Walsh and Selwyn Cobbo face Newcastle.
Canterbury have Jacob Preston back from a foot injury for their trip to North Queensland, against a Cowboys side who will also hold off a call on their five Origin stars.
Wests Tigers have likely lost hooker Apisai Koroisau to a calf injury for their clash with South Sydney, with Tallyn da Silva named in the No.9 jersey.
And Nick Meaney is back from his calf injury to play fullback for Melbourne against a Sydney Roosters side that has elevated Terrell May to starting prop with Jared Waerea-Hargreaves suspended.
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