Through surveillance video, police were able to identify one of the suspects as 27-year-old Mathew Phillip Sinson.
The discovery forced over 300 guests to be evacuated from the Hampton Inn Hotel in Center City around 5:30 a.m. Saturday morning.
Workers found chemicals and materials for the "shake-and-bake" method of producing the drug.
According to Chief Inspector Joseph Sullivan, hotel rooms are often used to produce the drug, a process that can result in toxic fumes and explosions.
Fire crews did not find any flames, but instead say fumes from a mobile meth lab in a third floor hotel room triggered the smoke detectors.
"Surprising," said Kaye Nimphie. "Who would ever think that would be going on?"
"A meth lab is kind of not what I was expecting," said Sam Nimphie.
It was an early morning adventure that was not on the out-of-towners itineraries.
Police say it is fortunate no one was hurt.
"With meth labs you're actually cooking chemicals, and that can cause an explosion," said Deputy Fire Chief Derrick Sawyer.
Nothing exploded, but police say they found multiple chemicals strewn across the hotel room in gallon containers.
"With a mobile meth lab you don't have large quantities, but enough quantities to do whatever you want to do for that time period," said Chief Sawyer.
No one was inside the portable lab when it was discovered, but investigators say Sinson was found inside his apartment nearby and was taken into custody.
A second suspect has not yet been identified but is also being sought.
Police say pop-up drug labs are new to Philadelphia, but nationally are becoming a troubling trend.
"They literally come to someone else's property, destroy it and leave," said Inspector Sullivan.
The hotel contracted a cleanup division to remove all of the potentially hazardous materials.