A night that started with a boycott by one set of Hammers fans ended with those that remained at the London Stadium booing the home side off the field as goals from Igor Thiago and Mathias Jensen secured a first away win of the season for capital Brentford, who should have won this Premier League match by a larger scoreline.
Nuno's first home match in charge coincided with a planned stay-away organised by supporters' groups in protest against the club's board.
Defeat meant the Hammers had lost their opening four home matches of a season for the first time in their history, with this reverse coming on the same day as former boss Graham Potter, sacked by the club last month, was named as the new manager of Sweden.
"Not good enough. Poor," said Nuno after a defeat that left West Ham in 19th place in the Premier League, with only basement club Wolves below them in the table. "Fairly, Brentford won the game, they were the better team.
"I think we are all concerned. You can see our own fans are concerned. Concern becomes anxiety, becomes silence. We have a problem."
The Portuguese boss, previously in charge of Premier League Nottingham Forest, added: "It's understandable. It's up to us to change. The fans need to see something that pleases them and they can support us and give us energy."
The only surprise on Monday was that it took Brentford 43 minutes to open the scoring.
Maximilian Kilman's woeful effort at clearing a routine ball over the top allowed Kevin Schade to nip in behind and hook the ball to Thiago.
Hammers keeper Alphonse Areola got a hand to his shot but the ball spun away and settled inside the far post.
Thiago, ruled out for most of last season through injury, found the net again before halftime, only to be denied by VAR for offside.
Thiago and Schade also hit the woodwork before Brentford finally made the game safe in stoppage time when Keane Lewis-Potter cut the ball back for fellow substitute Jensen to fire into the roof of the net.
"Very pleased," said Brentford boss Keith Andrews. "We approached the game really well. I had a good feeling the last few days, the vibe, the energy around the place. I thought we produced a really good performance."