On Sunday (AEST), City will face a Chelsea team which has been strengthened by the addition of Romelu Lukaku from Serie A champion Inter Milan, for a shade under £100 million ($188 million).
For much of the transfer window, City was expected to sign Harry Kane from Tottenham Hotspur, but that failed to come to fruition and it is instead looking for a squad-wide contribution to the goals account.
The Stamford Bridge test will give an indication of how well City can compete against fellow elite teams as it bids to retain the Premier League title.
With UEFA Champions League holder Chelsea adding Lukaku, Manchester United beating City to a deal for Cristiano Ronaldo, and Kane staying at Spurs for now, there are major clubs in England that have obvious focal points in attack.
Guardiola declared strikers to be unique in their sensibilities, saying: "They live outside of the bubble a team creates.
"They say, 'I am here to win the game'. We had privilege to have Sergio. These are the hardest players to take."
Aguero suffered with injuries during the closing stages of his 10-year City career, before leaving for LaLiga powerhouse Barcelona, and manager Guardiola found ways to cope without the leader of his attack, notably opting at times for a 'false nine', meaning his team was often stacked with attacking players but had no natural spearhead.
"We don't have this weapon like other teams have, like [Manchester] United, Chelsea or Tottenham. We have to use what we have as a team," Guardiola said.
"We don't have a player who scored 25 goals himself. We do it as a group and that is what we will try this season."
Guardiola has previously confirmed he would have liked to sign Kane, if he became available.
He reflected on his career as a coach and manager, pointing to always having had identifiable leaders and prolific scorers in his forward lines. Although Gabriel Jesus remains at City, Guardiola considers him a slightly different front player to a central striker.
"Always I had a striker in my career," the former Barcelona and Bayern Munich boss said.
"Like goalkeepers, strikers are the biggest specialists. I played with Samuel Eto'o [at Barcelona], maybe the best or one of the best strikers I ever trained. And [Thierry] Henry [at Barcelona].
"I don't know if he's a striker or what he is, but Lionel Messi was able to score a few goals. There was [Robert] Lewandowski, Thomas Muller [at Bayern Munich], Sergio here.
"Always I play with a striker. Gabriel [Jesus] likes to play more in lateral ways than central. We want it as a club because I think the club knows, not for me, that it needs a striker in the next years."
Guardiola still believes City is a formidable prospect, and the Chelsea game followed by next week's clash UEFA Champions League with Paris Saint-Germain are tantalising prospects.
"When our squad is fit – all of them – I know what we can do because I have seen it in previous years," he said.
"It is a privilege to go to London and play there and then Paris. You will not hear me one single second complain about this season or about the players I have."
City has won three of its past six Premier League away games against Chelsea (L3), more than it had in its previous 23 visits to Stamford Bridge in the top flight (W2 D8 L13).
Guardiola's side is looking to win back-to-back away top-flight games against Chelsea for the first time since January 1955.
In his managerial career, Guardiola has lost more games against Chelsea than he has versus any other opponent in all competitions (eight).
Indeed, the Blues could become the first team to win four consecutive matches against the Spaniard.