US Vice President Joe Biden, who heads to Europe freshly inaugurated for a second term, will be among officials, ministers, top military brass and experts from 90 delegations at the three-day annual get-together.
Other topics for the participants, who will include Russian Foreign Minister Sergei Lavrov, NATO Secretary General Anders Fogh Rasmussen and Israel's outgoing Defence Minister Ehud Barak, include cybersecurity, the euro crisis and energy issues, organisers said.
Deadly unrest in Egypt, developments in the Muslim and Arab world two years after the Arab Spring revolts, and NATO's plan to withdraw the bulk of its 100,000 combat troops from Afghanistan by the end of 2014 are also set to focus minds.
Iran's nuclear programme will be another talking point. Iranian Foreign Minister Ali Akbar Salehi and EU foreign policy chief Catherine Ashton, who represents world powers holding talks with Tehran, are due to attend the event.
Despite three meetings in 10 months, crunch talks by the so-called "P5+1" – the five permanent UN Security Council members and Germany – with Iran have failed to produce a breakthrough, and a new round has been delayed.
Israel and much of the West suspect Iran is trying to develop atomic weapons under the guise of its nuclear energy programme – a charge Tehran denies.
Similarly of concern for Israel and the international community is the 22-month conflict in Syria between forces of President Bashar al-Assad and rebels, which the UN says has claimed more than 60,000 lives.
Conference attendees in the southern German city will hear the latest assessments on the situation from Lakhdar Brahimi, the international peace envoy for Syria, as well as a Syrian opposition leader.
Jostling for the headlines with Syria is Mali, which has seen dramatic advances in recent days by French-led forces battling radical Islamists who seized the vast desert north of the west African country 10 months ago.
The French foreign and defence ministers may further discuss France's military mission in its former colony, after a donor conference raised $455.5 million for military operations in Mali as well as humanitarian aid.
"You only have to look at the map to realise the threat the jihadists in Mali pose to Europe," the Frankfurter Allgemeine Zeitung daily commented Tuesday.
"Nevertheless many in Europe still believe that al-Qaeda in Mali is just the Africans' problem, not ours," it added.
Germany, which has offered three transport planes to help in the Mali mission, has faced questions at home and abroad over why it has failed to match its economic might as Europe's effective paymaster with military commitments.
The Munich talks, sometimes dubbed the "Davos of Defence" coming hard on the heels of the annual gathering of the business and political elite in the Swiss Alps, will give the 60 German lawmakers and handful of ministers due to attend an opportunity to address the issue.
Biden, who attended the Munich conference in 2009, is first scheduled to hold talks with German Chancellor Angela Merkel in Berlin this time. Paris and London are also on his itinerary.
"I am of course very pleased that this core aspect of the Munich Security Conference, the transatlantic relationship... is still so strong," Wolfgang Ischinger, the former German diplomat in charge of the Munich conference, told reporters.
He also said he had addressed past criticism that the conference was made up of "old men" and doubled this year's participation by women to around 20 percent.
As well as Ashton, female participants are due to include the Kosovo president and Dutch and Rwandan foreign ministers, he said.