In his first South Asian foray since becoming prime minister, Wen will visit Pakistan from Tuesday to Thursday, then spend one day in Bangladesh and another day in Sri Lanka, before heading to India on 9 April for four days.
The visit underlines China's growing recognition of South Asia as a key area in its foreign policy initiatives, especially as Washington emphasises strengthening ties with New Delhi, analysts said.
"China seems continually worried about being contained by the United States," said Brad Glosserman, director of research for the Hawaii-based research group Pacific Forum CSIS.
"China is concerned and they're working to develop positive relations with these countries. They assume at some point there will be some competition between China and the US for pre-eminence in the region."
India had been sidelined by Beijing, which traditionally placed greater importance on relations with India's rival, Pakistan.
But with the cozy military partnership between Washington and Islamabad since the 11 September 2001 attacks, China is taking a new look at its priorities.
This comes as US Ambassador to India David Mulford wrote in an editorial last week that it is the United States' policy to help India become a major world power in the 21st century, something China is likely to see as an attempt by Washington to contain Beijing's rising power, analysts said.
"China's relations with India and Pakistan have shifted significantly in recent years," said Wu Guoguang, a China specialist at the University of Victoria's Centre for Asia-Pacific Initiatives.
"In the past China always stood firmly on Pakistan's side when there are conflicts between Pakistan and India. In recent years, they are more balanced. ... They are considering the new geopolitical situation."
China and India have gone to war over border disputes, but relations improved dramatically after a visit to China in 2003 by then-prime minister Atal Behari Vajpayee during which India acknowledged Tibet as a part of China and China gave up its territorial claim over the tiny Indian state of Sikkim.
Improving ties with India is likely to help Beijing maintain its traditional influence over Pakistan, a country it needs onside to fight separatism from Muslims in its northwest Xinjiang region, analysts said.
"China needs to have good relations with a major neighboring Muslim country like Pakistan in order to deal with its domestic Muslim problem," said Wen Fude, director of Sichuan University's South Asia Research Institute.
In Pakistan, Wen's focus will be on maintaining cooperation in fighting separatism.
Chinese vice foreign minister Wu Dawei said on Friday that China and Pakistan's partnership on anti-terrorism - a term Beijing uses to refer to separatism - has been "very effective" and that Beijing was "satisfied" with Islamabad's help.
"I believe the two sides should work closely with each other to maintain regional peace, stability and security," Wu said.
China also is looking to Pakistan as a transit route for oil from the Persian Gulf region.
In return for Islamabad's assistance, China has been a major weapons supplier for Pakistan, which also receives economic assistance from Beijing, such as loans and expertise in building infrastructure, including highways.
Economic initiatives will feature in Wen's tour.
While China and India are economic competitors, both have put aside their remaining border disputes to focus on increasing trade and improving ties.
"China feels that as long as economic cooperation is increasing, many problems can be resolved," Wu said.
India's ambassador to China Nalin Surie told the Xinhua news agency the two countries were "rediscovering each other" and that the visit would "mark a new phase" in bilateral relations.
A free trade area was being proposed between the two countries. If achieved, it will be the largest free trade area in the world in terms of market size.
A series of agreements on politics, trade, technology and education are expected to be signed during Wen's four-nation tour.