Barcelona start their campaign at Elche on Sunday, with Real Madrid beginning their season at Espanyol the previous day. The return of Jose Mourinho to the Madrid dugout has added another layer to one of European football's biggest rivalries.
Flick guided Barcelona to successive LaLiga titles in his first two seasons and believes his squad is ready to compete again.
"We have an incredible team, with a lot of quality," Flick told Barcelona supporters ahead of their final pre-season friendly against Al Ahly.
"We are ready to work hard day after day and to fight for all the titles."
The biggest change to Flick's squad is the arrival of Rodri from Manchester City. The Spain midfielder is expected to give Barcelona greater control in midfield while also providing extra protection for a defence that has sometimes looked vulnerable.
Rodri also brings vast experience of winning major trophies, something Barcelona hope can help them end their wait for another Champions League triumph.
"I'm here to compete for everything, for big things like the Champions League," Rodri said after being presented as a Barcelona player.
However, Barcelona have also lost Robert Lewandowski and Ferran Torres, leaving Flick with an important problem to solve in attack.
Sporting director Deco admitted replacing Lewandowski's goals will be particularly difficult after Barcelona failed to reach an agreement for Julian Alvarez.
"What Ferran did we can cover with the signings, but what Robert did is more difficult," Deco said.
"We have internal solutions, but we will make another move; we'll try and find the best solution."
Anthony Gordon and Karim Adeyemi have joined Barcelona and both offer the pace and energy needed for Flick's pressing style. Dani Olmo and Raphinha can also play through the middle, giving the coach several options if the club does not sign another traditional striker.
But much of Barcelona's attacking threat will again depend on Lamine Yamal.
The teenager has already become one of the team's most important players and Barcelona will hope he can enjoy a full season at his best after injuries disrupted parts of his previous campaign.
Flick will also face a different challenge from Real Madrid this season. Mourinho's return to the Spanish capital is likely to add extra intensity to a rivalry that became particularly heated during his first spell at Madrid between 2010 and 2013.
Barcelona have dominated the domestic battle in recent seasons, but Madrid have strengthened and will be determined to close the gap.
Flick therefore starts his third campaign with plenty of questions to answer. If Rodri brings the expected stability, Yamal maintains his extraordinary form and Barcelona find enough goals without Lewandowski, they will have a strong chance of retaining their La Liga crown.