Hosting a one-day summit attended by more than two dozen African leaders and European Union officials, Meloni outlined a series of initiatives, pledging an initial €5.5bn, including state guarantees.
Meloni said the summit had been a success that had produced many areas of potential cooperation, particularly with regards to energy.
"We are only at the beginning, there is a very long road ahead of us. This day is a restart," she said in her closing remarks.
However, there was a note of discord from some of those present, with Moussa Faki Mahamat, chairman of the African Union Commission, saying he wished Africa had been consulted first on priorities and emphasising the need to honour commitments.
"I want to insist here on the need to move from words to actions. You can well understand that we can no longer be satisfied with mere promises that are often not kept," he said, standing alongside Meloni in Italy's ornate Senate.
In a news conference after the summit, Meloni acknowledged that it was important now to ensure that work began to deliver projects that would make a difference on the ground.
Among the African leaders present were the presidents of Tunisia, Senegal, Kenya, the Republic of Congo and Somalia. In all, 45 African states were represented at various levels.
Critics have said that heavily indebted Italy cannot hope to compete with the likes of China, Russia and Gulf states, that are all looking to boost their presence in Africa, which is home to many of the world's natural resources.
While Rome claims ownership of the plan, which it has named after the late Enrico Mattei, who founded state oil company Eni, Meloni said her government would look to help from the private sector and international bodies such as the European Union.
Meloni has made the Mattei plan a central plank of her foreign policy since taking office in late 2022.
Energy needs lie at the heart of the initiative, with Rome looking to serve as a gateway into European markets for natural gas from Africa that has become vital after Russia's invasion of Ukraine made diversification of supplies a priority for the EU.
Eni, Italy's largest importer of natural gas, has already countered lower Russian supplies by shipping increased volumes from Africa, where it has had a presence for decades.
The company has said Algeria, Egypt and Libya will be Italy's main gas suppliers for the next few years.
But Meloni also said Europe had to bolster industry and agriculture in Africa to strengthen local economies as a way of persuading disaffected young Africans from migrating north.
Some 157,600 boat migrants reached Italy last year, the largest number since 2016, undermining Meloni's electoral pledge to halt the flow of unauthorised arrivals.
Most departed from North African countries such as Tunisia and Libya, many fleeing poverty and conflict in sub-Saharan Africa and the Middle East.
"Mass immigration will never be stopped, human traffickers will never be defeated if we do not address the many causes that push a person to leave their home," Meloni told the summit. "This is exactly what we intend to do."
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