Facing war on the 27-nation bloc's eastern flank, tensions in the Middle East, sluggish competitiveness and a fraught political environment, the European Union's top executive team has its work cut out for it.

Here are some of the main issues the powerful body led by the 66-year-old German politician will have to grapple with in its first 100 days:

- Donald Trump -

Von der Leyen is once again starting her mandate with "an exogenous shock to deal with", said Simone Tagliapietra, of Brussels-based think tank Bruegel.

Covid-19 struck shortly after she started her first stint in 2019. This time, it's Donald Trump returning to the White House that is jolting Brussels into action.

The EU's executive arm will have to swiftly come up with cohesive plans on trade and defence to help shield the bloc from a US president set on rebalancing trade deficits through tariffs, and potentially less committed to European security.

Part of this could see the EU vow to buy more military equipment -- and gas -- from the United States to bolster its defences and avoid a trade war, suggested Tagliapietra.

- The economy -

The former German defence minister said the prime focus of her new term should be revamping EU economic competitiveness, avoiding what Mario Draghi, a former Italian prime minister, has described as the "slow agony" of decline.

A "competitiveness compass" framing the commission's strategy will be the body's first major initiative, von der Leyen told parliament on Wednesday.

The bloc is failing to keep up with the United States and faces mounting competition from China amid an array of challenges including low productivity, slow growth, high energy costs and weak investments.

To that aim, the EU will seek to boost innovation, support the decarbonisation of its economy by investing in clean power to bring down energy prices, and diversify supply of raw materials, she said.

Cutting red tape and creating a savings and investments union to help companies access capital to pour into research for innovation are also top of the agenda.

- Agriculture blues -

One of the first hot potatoes the commission will have to deal with is a controversial trade deal with South America's Mercosur bloc.

Farmers, especially in France, are up in arms as they fear being undercut by cheaper produce from their less-regulated South American counterparts.

The EU is looking to finalise the pact with Brazil, Argentina, Paraguay and Uruguay during a summit in Montevideo next month.

But France and like-minded countries are hoping to derail plans to create the world's largest free trade zone.

Von der Leyen has also promised to lay out a "vision for agriculture and food" that would ensure "competitiveness and sustainability" for the farming sector.

Tractors have repeatedly blocked the streets of Brussels in recent years, with farmers upset at cheap imports, low margins and the burden of environmental rules.

- Defence -

Stepping up Europe's defences has been a priority since Russia invaded Ukraine in 2022 -- but Trump's re-election has added urgency.

European defence spending has been too little and too disjointed in recent decades to keep up with Russia and China, according to the commission.

"We have no time to waste," von der Leyen said on Wednesday, noting that Moscow is spending up to nine percent of GDP on defence against the EU's 1.9 percent.

She has estimated that the bloc will need to invest 500 billion euros ($525 billion) over the next decade.

For the first time, the EU will have a defence commissioner -- Andrius Kubilius of Lithuania -- who along with new foreign policy chief Kaja Kallas, has been charged with setting out a roadmap for European defence in the first 100 days.

But so far, any calls for a joint borrowing scheme, similar to how the bloc financed its post-pandemic recovery, remain divisive.

- Immigration -

Irregular border crossings detected into the European Union are down 43 percent this year after an almost 10-year peak in 2023.

Yet migration is high on the political agenda following far-right gains in several countries.

In October, EU leaders called for urgent new legislation to increase and speed up returns and for the commission to explore "new ways" to counter irregular migration.

Von der Leyen has promised to swiftly put a proposal on the table, just months after the bloc adopted a long-negotiated reform of its asylum policies.