In a speech to the Australian Institute of International Affairs on Monday, Penny Wong said vast steps had been made to bolster relations with countries in the Indo-Pacific, citing multiple treaties being signed with allies like Indonesia and Papua New Guinea.
Yet difficulties persist and Australia must remain vigilant.
"We have advanced every relationship we have in our region. But that doesn't mean that our strategic environment is getting any easier," she said in the address.
"The change in the regional landscape is permanent. The disruption - the contest - is permanent.
"With so much activity and contest, things may not go Australia's way every time. But we will keep pressing our national interest in the contest every day."
Senator Wong said while relations between China and Australia had been improving in recent years, issues remain, warning the Asian power would try to reshape the region "according to its own interests".
The foreign minister indicated Australia still had a crucial role in Southeast Asia and the Indo-Pacific.
"Our overriding responsibility as a middle power of the Indo-Pacific is to support peace, stability and prosperity in this region. The Indo-Pacific is where the world's future is most being shaped. It is where we have the most on the line," she said.
"Australia has sought to redefine our relationships with our region. Listening, not imposing. Consulting, not controlling."
The comments from Senator Wong followed a speech from Prime Minister Anthony Albanese, who also said the steady role of diplomacy within the region had been beneficial.
"Geographically centred in this region, we are uniquely placed to further our shared interests as well as to demonstrate solutions and strategies to solve shared problems," the prime minister said on Monday at the APEC Study Centre.
"Perhaps now more than ever that is the role of a middle power."
Australia's political leaders have celebrated the lifting of US tariffs on beef and other agricultural goods, along with a major agreement on critical minerals.
Mr Albanese's team will soon shift its focus to eliminating all remaining trade barriers with the US.
The prime minister also has his sights on advancements in clean energy, artificial intelligence and a broader evolution in global trade.
"All of these represent Australian challenges and Australian opportunities. But not uniquely so," he said.
"They are global in scale and they connect us all. That is why we cannot find our prosperity - or our place in the world - by only looking inward."