All-rounder Rachin Ravindra could also miss the Group A match as he continues to recover from a blow to his forehead sustained during a tri-series match in Lahore earlier this month.
Ferguson, who suffered a hamstring injury in a T20 tournament in the United Arab Emirates earlier this month, felt pain in his right foot after bowling in Sunday s warm-up match against Afghanistan.
An initial medical assessment suggested the 33-year-old would not be fit to take part in the entire tournament, New Zealand Cricket (NZC) said.
New Zealand have decided to send him home and bring in Canterbury Kings fast bowler Kyle Jamieson, who will not reach Pakistan in time for Wednesday s match.
"We re really disappointed for Lockie," head coach Gary Stead said in the statement issued by the NZC.
"Lockie is a key part of the bowling group and brings a lot of major tournament experience and we know how much he was looking forward to representing New Zealand at another major event."
Jamieson returned to domestic cricket in December after 10 months on the sidelines due to a stress fracture in his back.
"Kyle brings plenty of pace and extra bounce which will suit the conditions here in Pakistan," Stead said of Jamieson, who will be available for New Zealand s second Group A game against Bangladesh on Feb. 24.
Though on a high after winning the tri-series in Pakistan beating the hosts in Friday s final, New Zealand are also without quick Ben Sears due to a hamstring injury.
India s Jasprit Bumrah, Anrich Nortje of South Africa and Australian duo Pat Cummins and Josh Hazlewood are among other fast bowlers to miss out on the Champions Trophy with injuries.
New Zealand are also waiting to hear about the fitness of spin-bowling all-rounder Ravindra, who suffered a nasty blow after losing sight of the ball in the floodlights while attempting to catch it.
"He s had a couple of hits, but ... we ll take medical advice around it understanding with a hit in the head the way he got, and stitches to his forehead as well," Stead later told reporters.
"We will be taking a cautious approach with him. If he doesn t play this game, we expect he ll be right for the next one."
Pakistan captain Mohammad Rizwan confirmed Babar Azam would continue to open the innings like he did in the recent tri-series.
"Babar is our most solid player, technically. He will bat at the top," Rizwan told reporters.
New Zealand beat Pakistan twice in the recent tri-series but Rizwan was hopeful they would be third time lucky.
"We have identified our shortcomings and work on them. We are confident we will not repeat those mistakes tomorrow."
