Named the Ken Irvine Medallist following his 24 tries during the Telstra Premiership season, Isaako's two tries gave Michael Maguire's side a commanding early lead that they wouldn't look back from, to secure their first shut-out win on home soil in over two decades.
Playing their first game since a narrow defeat to Australia in last year's World Cup semi final, New Zealand's combination of power through the middle and quality work from their outside backs was simply irrepressible as Samoa struggled to generate sustained attacking pressure or go-forward.
Captain James Fisher-Harris, Moses Leota and Joseph Tapine all starred early on for the Kiwis - along with a try-scoring Nelson Asofa-Solomona off the bench.
Fullback Charnze Nicoll-Klokstad made an impact early for the Kiwis with his clever cut-out sending Isaako over for the first points of the game after 13 minutes.
The 2023 Ken Irvine Medallist was streaking away down the sideline not long after following a mazy run from Matt Timoko, with his Canberra teammate in Tapine sending Jahrome Hughes over at the end of the set to extend the lead to 12-0.
New Zealand's third try in 11 minutes threatened to open the floodgates, with Isaako the beneficiary again of some clever work in the build-up - wrestling his way past Storm young gun Sua Fa'alogo to push the lead out to 18-0, which is how it would remain at the interval.
Asofa-Solomona would make it a perfect start to the second half for New Zealand when he crashed over from close range before Isaiah Papali'i made it 28-0 with half an hour still to play after racing through to collect a Hughes grubber to score.
Ronaldo Mulitalo crossed in the 60th minute - doubling up late on for the first brace of his international career - with late tries to Briton Nikora and Fisher-Harris took the winning margin to 50.
An obstruction denied Tommy Talau Samoa's best points-scoring opportunity of the game when Daejarn Asi was ruled to have taken an advantage behind the lead runner.
It was the Kiwis first shut-out win in an international fixture since a 48-0 win over France at the 2013 Rugby League World Cup.
Earlier, the Kiwi Ferns beat Mate Ma'a Tonga 28-10 at Eden Park in Auckland thanks to a hat-trick of tries to Abigail Roache.
New Zealand led 10-6 at half time.
Amelia Pasikala scored a try early in the second half and the floodgates opened, with Tonga struggling to slow New Zealand down.
Kiwi Ferns centre Mele Hufanga was also outstanding, picking up the MVP.