Van Nistelrooy accepts Man Utd lack a clinical striker
Only struggling Southampton and Crystal Palace have scored fewer Premier League goals this season than United's nine in 10 games.
A lack of killer instinct in front of goal played a big part on Erik ten Hag's dismissal as manager last month.
United have spent more than £100 million ($129 million) in bringing in Hojlund and Zirkzee over the past two summer transfer windows.
Hojlund has scored twice in 11 games during an injury-hit start to the season, while Zirkzee has only found the net once in 16 matches since joining from Bologna.
By contrast, Van Nistelrooy remains a legend at Old Trafford for his clinical finishing, scoring 150 goals in 219 appearances for the English giants during his playing career.
"I agree that when you want to be a successful side in the Premier League and in Europe, and that's what the build is all about, you’re going to need a certain amount of goals," Van Nistelrooy said ahead of his final game in charge against Leicester on Sunday.
"That is facts in football and that's why the best teams in the world have those players.
"At the moment we have players that get a certain amount of goals or assists but they are obviously at an age where they still have to be developed, and there's the potential that they will be, the belief is there that they can."
Van Nistelrooy has steadied the ship with victories over Leicester, to reach the League Cup quarter-finals, and PAOK in the Europa League on Thursday.
United also held high-flying Chelsea to a 1-1 draw last weekend in the Dutchman's only Premier League match in charge so far.
Van Nistelrooy already had senior managerial experience from one season at PSV Eindhoven prior to returning to his former club as an assistant to Ten Hag in July.
Ruben Amorim will bring his own coaching staff with him from Sporting Lisbon when he takes over next week.
Van Nistelrooy, though, wants to stay on as an assistant once his caretaker spell comes to an end.
"I knew that coming to Manchester United was for me a special occasion, where I felt I want to be part of this journey with the club, in an assistant role," said Van Nistelrooy.
"I have clear ambitions to manage. I made the decision to sign a two-year deal as an assistant and I'm still in that frame of mind, to be fair, to stay in that capacity."