Pompeo said the United States "will oppose any country" which seeks to dominate the region in what appeared to be a reference to Beijing amid heightened tensions in the South China Sea.
"Like so many of our Asian allies and friends, our country fought for its own independence from an empire that expected deference," Pompeo said. "We thus have never and will never seek domination in the Indo-Pacific, and we will oppose any country that does," he added.
Countries in the region have been worried by Trump's "America first" policy, withdrawal from the Trans Pacific Partnership trade deal, and pursuit of a trade conflict with China that threatens to disrupt regional supply chains.
The United States first outlined its strategy to develop the Indo-Pacific economy at an Asia-Pacific summit last year.
"Indo-Pacific" has become known in diplomatic circles as shorthand for a broader and democratic-led region in place of "Asia-Pacific," which from some perspectives had authoritarian China too firmly at its center.
Among the new investments outlined by Pompeo, the United States will invest $25 million to expand U.S. technology exports to the region, add nearly $50 million this year to help countries produce and store their energy resources, and create a new assistance network to boost infrastructure development.
China's way, US way
Speaking to reporters ahead of the speech, Brian Hook, senior policy adviser to Pompeo, said the United States was not competing with China's mostly state-led infrastructure initiatives.
"It is a made-in-China, made-for-China initiative," Hook told reporters on a conference call. "Our way of doing things is to keep the government's role very modest and it's focused on helping businesses do what they do best."
Critics of Beijing's Belt and Road Initiative, which aims to recreate the ancient Silk Road, say it is more about spreading Chinese influence and hooking countries on massive debts. Beijing says it is simply a development project that any country is welcome to join.
Hook said Washington "welcomed" Chinese contributions to regional development, but said it wanted China to adhere to international standards on transparency, the rule of law and sustainable financing.
"We know that America's model of economic engagement is the healthiest for nations in the region. It's high-quality, it's transparent and it is financially sustainable," Hook said.