Casey, leading in polls as he tries to unseat the Senate's third-ranking Republican, said the United States is in "worse shape" in regard to Iran and North Korea because of President Bush's policies.
"I think this administration should make sure it listens to the military experts, something the Bush administration has not done very well in regards to Iraq," said Casey.
When pressed about what line would have to be crossed before he would vote to take military action against Iran or North Korea, Casey said he would have to rely on intelligence and military experts to help make the decision.
"We cannot sit here tonight and draw a line," Casey said.
Santorum said of the potential development of nuclear weapons in Iran: "I understand this situation."
"If we are to believe that they are close to developing a nuclear weapon, I would do, I would strike, without question. ... Iran cannot have a nuclear weapon. This is not North Korea, which I believe would use it more for defensive purposes," Santorum said.
Santorum, who has been a staunch defender of the decision to invade Iraq, said a second look would be a good thing. He praised the work being done by former GOP Secretary of State James A. Baker III to study it. He also said partitioning Iraq "may be a change of course that we need."
The two also differed on Defense Secretary Donald Rumsfeld. As he has before, Casey said Rumsfeld should be fired. "We need new leadership when it comes to Iraq," Casey said.
Santorum defended Rumsfeld, saying, "He follows policy. He doesn't make policy."
Casey, the state treasurer, told Santorum on Tuesday he planned to release his IRS filings for the last five years, and asked Santorum to do the same. Santorum said he would.
The debate at the National Constitution Center was much less contentious than a debate last week in Pittsburgh, where the two bickered throughout.
Casey has accused Santorum of being part of the problem in Washington and voting with President Bush 98 percent of the time. Santorum has said Casey spends too many days away from his state treasurer's office and does not address issues.
Immigration, Social Security and the environment were also discussed Monday night.
Santorum said Casey supported environmental policies that would hurt manufacturing in Pennsylvania, while Casey said it was "dinosaur" thinking by Santorum that all policy that is good for the environment is bad for jobs. Casey also accused Santorum of not recognizing the danger of global warming.
Last month, a poll showed Casey held a 14-point lead over the incumbent among 933 likely Pennsylvania voters. The Quinnipiac University Poll had a sampling margin of error of plus or minus 3 percentage points.