President Joe Biden will confront a kaleidoscope of challenges when he travels to the Middle East this week, his first trip there since taking office.

With the American wars in Iraq and Afghanistan in the rearview mirror, the United States is reassessing its role in the region at a time when its focus has shifted to Europe and Asia.

In his own words, Biden said he will seek to "start a new and more promising chapter of America’s engagement" in the Middle East, writing in a Saturday op-ed for the Washington Post: "This trip comes at a vital time for the region, and it will advance important American interests."

The president noted in his opinion piece that while the region is "less pressurized and more integrated" than when he visited nearly two decades ago, there are still a number of challenges to overcome – many of which Biden will address in face-to-face meetings with his counterparts in countries including Israel and Saudi Arabia. 

Some of those issues, Biden wrote, inlcude "Iran’s nuclear program and support for proxy groups, the Syrian civil war, food security crises exacerbated by Russia’s war against Ukraine, terrorist groups still operating in a number of countries, political gridlock in Iraq, Libya and Lebanon, and human rights standards that remain behind much of the world.

"We must address all these issues," the president wrote in his WaPo article. "When I meet with leaders from across the region, I will make clear how important it is to make progress in these areas."

Here is look at some of the major issues that will be at play during Biden’s trip:

Biden will become the first U.S. president to travel directly from Israel, his first destination, to Saudi Arabia, his last stop before returning to Washington. The itinerary is a reflection of friendlier relationships between Israel and its Arab neighbors, a tectonic shift that is reshaping the region’s politics.

Under President Donald Trump, Israel normalized relations with countries such as the United Arab Emirates through the Abraham Accords. Although no one expects Israel and Saudi Arabia to announce formal diplomatic ties during Biden’s trip, more incremental steps could be taken, such as allowing Israeli commercial flights to cross over the kingdom en route to other countries nearby.

In addition, there’s already a surge in security cooperation being presided over by the U.S. military’s Central Command, which oversees operations in the region. John Kirby, a national security spokesman for the White House, said the nascent military partnership is intended to foster a regional air defense system that could protect against Iranian ballistic missiles and drones.

The threat of Iran is one of the primary incentives for Israel and Arab countries to work more closely together, and the issue will likely be a top focus for Biden’s meetings. Israel views Iran as its greatest threat, and Sunni Arab countries consider Shiite Iran as a dangerous competitor for regional power.

A key question is finding the best way to prevent Iran from developing a nuclear weapon, which it’s believed to be closer than ever to achieving. Biden wants to rejuvenate the nuclear deal that was reached by President Barack Obama in 2015 and abandoned by Trump in 2018, but negotiations appear to have stalled.

Israel, which is widely believed to be the only nuclear-armed state in the region but does not acknowledge having such weapons, was opposed to the deal. It didn’t like that the agreement limited Iran’s nuclear enrichment for only a set period of time, nor did it address Iran’s ballistic missile program or other military activities in the region. Now Israel is calling for increasing sanctions to pressure Tehran into agreeing to a more sweeping accord.

Biden is expected to visit one of Israel’s missile defense installations as he tries to reassure Israelis that the U.S. is committed to the country’s protection.

Even though Israel is building closer ties to Arab countries, there’s been no progress toward resolving its decades-long conflict with the Palestinians.

In fact, some Palestinians feel abandoned by Arab leaders who have reached their own deals with Israel through the Abraham Accords. That came without securing progress toward the Palestinians’ goal of an independent state in Israeli-annexed east Jerusalem, the occupied West Bank and Gaza, lands Israel seized in the 1967 Mideast war.

And there are increasing doubts that a two-state solution is even possible at this point because Israel has spent decades expanding settlements that are now home to hundreds of thousands of Jewish settlers. Israel blames the continuing conflict on Palestinian violence and the refusal of Palestinian leaders to accept past proposals that it says would have given them a state.

Biden plans to visit with Mahmoud Abbas, the head of the Palestinian Authority, in Bethlehem during his trip. But it’s unlikely that there will be an opportunity to prod either him or Israeli Prime Minister Yair Lapid to reopen talks. The Palestinian Authority, which administers parts of the occupied West Bank, has grown increasingly unpopular and autocratic in recent years. Lapid is a caretaker prime minister serving while Israel braces for another round of elections later this year.

During a press briefing on Monday, national security adviser Jake Sullivan said Biden "will meet with the prime minister, the president, the leader of the opposition as well as attend the reception with a number of other key figures. He will also have the opportunity to receive a briefing on Israel's missile defense capabilities, including the U.S.-supported Iron Dome." 

"President Biden will also meet with President Abbas and attend a health event with Palestinian civil society," Sullivan added of the upcoming trip.

Biden will likely be confronted with more fallout over the death of Palestinian-American journalist Shireen Abu Akleh, who was killed two months ago. An analysis overseen by the United States suggested that she was shot by Israeli soldiers who were conducting a raid nearby, but it stopped short of drawing a definitive conclusion. The murky outcome led to more anger than clarity.

The treatment of journalists will also be a focal point when Biden visits Saudi Arabia. U.S. intelligence believes that the kingdom’s crown prince, Mohammed bin Salman, likely approved the killing of Jamal Khashoggi, a U.S.-based writer for the Washington Post who was critical of the regime. The murder was carried out by agents who worked for the crown prince, and it took place inside the Saudi consulate in Istanbul in 2018.

While the president himself has not spoken with Khashoggi's family, Sullivan said Biden "has been focused on this issue from the beginning," adding: "Our goal has been to recalibrate, to not rupture the relationship with Saudi Arabia, to end the blank check policy, and to seek accountability." 

Dozens of activists, writers, moderate clerics and economists remain imprisoned for their criticism of Mohammed bin Salman. The few who’ve been released, like blogger Raif Badawi and women’s rights advocate Loujain al-Hathloul, face yearslong travel bans and cannot speak freely. Some senior members of the royal family have been arrested or had their assets seized, and others were forced into exile.

Biden noted the criticism in his WaPo op-ed, writing in part: "I know that there are many who disagree with my decision to travel to Saudi Arabia. My views on human rights are clear and long-standing, and fundamental freedoms are always on the agenda when I travel abroad, as they will be during this trip, just as they will be in Israel and the West Bank."

Despite the crackdown in Saudi Arabia, the crown prince has also been credited with reforms. Saudi Arabia looks and feels starkly different than just five years ago, when religious police still roamed the streets chastising women for wearing bright nail polish in malls, enforcing gender segregation in public places and ordering restaurants to turn off background music. Women can now drive, travel abroad without the permission of a male relative and attend sporting events in stadiums once reserved solely for men. Movie theaters and concerts, including one with pop star Justin Bieber, have government backing, a major change after decades of ultraconservative Wahhabi influence.

Biden will likely face pressure to temper his criticism of Saudi Arabia’s human rights record to persuade the kingdom and its neighbors to pump more oil and alleviate months of sky-high prices at the gas pump.

Energy analysts say drivers shouldn’t get their hopes up. “If the public is looking for lower gasoline prices after this trip, I think they’re bound to be disappointed,” said Samantha Gross, director of the energy security and climate initiative at the Brookings Institution.

The Saudis, among the biggest energy producers in the world, are already producing near their full capacity of 11 million barrels of oil per day. And members of OPEC+ nations, including the Saudis, are likely to be cautious when it comes to demands from the U.S.

In 2020, as the coronavirus pandemic severely scaled back travel, Trump urged OPEC+ to scale back production as the U.S. oil industry wobbled. Now, as the Russian invasion of Ukraine has driven up prices, Biden wants OPEC+ to produce more even though there are fears of a global recession around the corner.

Elevated oil prices are simply good business for the Saudis, the de facto leader of OPEC+. The kingdom reported that the value of its crude exports were about a $1 billion per day in March and April, a 123% increase compared to the same period in 2021.

Another partnership is also taking shape while Biden is traveling in the Middle East. He’ll be convening a virtual summit with the leaders of Israel, India and the United Arab Emirates under a new moniker — the I2U2.

It might seem like an unlikely collection of countries, but there are hopes for productive collaboration. Navdeep Suri, a former Indian ambassador to the UAE, said the initiative is intended to bring together Israeli technology, UAE capital and Indian skills.

“We are seeing a churn in the region and for India, it is better to be on the table rather than off the table,” he added.

Ned Price, a spokesman for the U.S. State Department, said there’s a lot of opportunity for deepening relationships.

“There are a number of areas where these countries can work together, whether it’s technology, whether it’s trade, whether it is climate, whether it’s COVID, and potentially even security as well,” he said.

Talmeez Ahmed, India’s former ambassador to Saudi Arabia, suggested there would be limits to security cooperation, and he’s skeptical about the new initiative.

Ahmed noted Israel has “said it is against Iran. There is no way India will join an alliance against Iran.”