Both picked up injuries sustained in the opening 17-16 win over England, with Nightingale an ankle injury and Waerea-Hargreaves a knee complaint.
Replacing them are Gerard Beale on the wing and Greg Eastwood on the bench, with Adam Blair promoted to the starting lineup.
“It’s tough losing players of Nighty’s [Nightingale] and Jared’s [Waerea-Hargreaves] talent and experience,” Kiwis coach David Kidwell said.
“We are fortunate to have quality reinforcements who understand what international football is all about.”
Kidwell, who has been a strong advocate for the importance of team culture, has been impressed with the injured pair’s attitude.
“They are both terrific players and they are wonderful people. They have been terrific examples of what ‘Te Iwi Kiwi’ is all about.
“Both Bealy [Beale] and Beasty [Eastwood] have been pushing hard for spots all tour, as well as the young guys in the team. As a coach, it’s fantastic to know that everyone is working hard.
“I have complete confidence in all the players in our squad. That’s why they were picked.”
The full NZ Kiwis team is:
Number Name Club Kiwi #
1 Jordan Kahu Brisbane Broncos 790
2 Gerard Beale Cronulla Sharks 767
3 Solomone Kata NZ Warriors 797
4 Shaun Kenny-Dowall Sydney Roosters 746
5 Jordan Rapana Canberra Raiders 798
6 Thomas Leuluai NZ Warriors 704
7 Shaun Johnson NZ Warriors 774
8 Jesse Bromwich (c) Melbourne Storm 775
9 Issac Luke NZ Warriors 749
10 Adam Blair Brisbane Broncos 732
11 Kevin Proctor Melbourne Storm 771
12 Tohu Harris Melbourne Storm 778
13 Jason Taumalolo North Queensland Cowboys 786
14 Lewis Brown Manly Sea Eagles 762
15 Martin Taupau Manly Sea Eagles 785
16 Manu Ma’u Parramatta Eels 795
17 Greg Eastwood Canterbury Bulldogs 737
18 Joseph Tapine Canberra Raiders –
19 David Fusitu’a NZ Warriors