With seven rounds of the regular season remaining Penrith find themselves eight points clear at the top of the ladder, while the Sharks have climbed to third after beating the Cowboys last up.
Cronulla are riding a five-game winning streak and will be full of confidence, while Penrith should benefit from refreshing a number of their top line stars last weekend ahead.
The last time they met in Round 14 last year it was Cronulla who came away with a late 19-18 victory, but prior to that the Panthers won the past four head-to-head clashes.