The attack -- the deadliest of three that occurred in Saudi Arabia during in a 24-hour span -- killed four security staff in a parking lot outside the Prophet's Mosque, the grand place of worship that was created in an expansion of the original humble mosque built by the Prophet.
For many Muslims worldwide, as Haroon Moghul, senior fellow at the Center for Global Policy, writes
, this was "an assault on Islam itself."
The Medina attack prompted an outpouring of outrage and condemnation, prompting hashtags such as #PrayForMadinah and #bombingattheholysiteofmedina to trend on social media.
Many tweets in Arabic apologized to the Prophet Mohammed for the attackers having struck in the city, seen in Islamic tradition as a safe haven for the Prophet after he led the persecuted early Muslim community there from Mecca.
"O Messenger of Allah...They did not respect the prestige of your residence in their neighbourhood," wrote one Twitter user.
Many expressed the view that no Muslim could have targeted one of the religion's holy cities, or were quick to distance Islam from the attacks.
"Three bomb attack in 24hrs in the holiest place for Muslims," wrote one Twitter user. "(H)ow can anyone relate Islam to terrorism?!"
Another wrote that the mosque was "one of the most peaceful places on earth."
"Terrorism has no religion!"
"I couldn't even speak loudly there.. How can you carry a bomb there!! Muslim cannot do it," wrote Mahammed Naushad.
Others pointed out that many of the recent Ramadan attacks occurred in Muslim countries.
"Before blaming Muslims for ISIS, remember that ISIS terrorist attacks is targeting more Muslims than any other groups. #ISISAttackingMuslims," wrote Reem AlHarmi.
Hashtags also circulated calling on people to change their profile picture to the Saudi flag in solidarity, while other responses suggested a tipping point may have been reached in the Muslim world's response to terrorism the wake of the attack.
"Saudi has to call for an Islamic summit to fight ISIS under the banner of defending the burial place of the Prophet Muhammad and every Muslim will respond," wrote Saudi journalist Jamal Khashoggi.
The Sunni kingdom's Shia nemesis, Iran, was among the governments denouncing the attack.
"There are no more red lines left for terrorists to cross," Iranian Foreign Minister Mohammad Javad Zarif said on Twitter. "Sunnis, Shiites will both remain victims unless we stand united as one."
Month of carnage
While there has been no claim of responsibility so far for the Saudi attacks, analysts believe that, like a number of other attacks this Ramadan, they could be the work of ISIS or its sympathizers.
For the vast majority of Muslims, the holy month is a time for fasting, prayer and good actions, but Islamist terror groups see it as an especially auspicious time to launch attacks.
ISIS, facing the loss of its territory in Iraq, had called on its followers to launch attacks this Ramadan, and the response has been a string of deadly incidents around the world.
As well as the attacks in Baghdad, Istanbul, Dhaka and Saudi Arabia, extremists have struck in Yemen
ISIS has claimed responsibility for some of these attacks, and authorities believe other perpetrators were inspired by the terror group.
The attacks continued into Tuesday, when a suicide bomber tried to enter police headquarters in the central Javanese city of Solo, Indonesia, wounding a police officer, authorities said.
An Indonesian official said it was too early to know who was behind the attack.
Tim Lister, a CNN expert on Middle East affairs, said the Saudi attacks fit the "modus operandi" of ISIS and that the kingdom, a key U.S. ally in the Muslim world, represents "a real target to show" ISIS "can punch above its weight."
"Saudi Arabia is a big target for them. They have a lot of Saudi fighters in their ranks. They regard the Saudi monarchy as having betrayed Islam."
Peter Bergen, CNN national security analyst, said that ISIS had called for attacks during Ramadan and "now we have them."
But while the attack on Medina undercuts the Saudi royal family's claim to be the "protectors of the two holy places," it was hard to imagine a target more counterproductive to any Islamist terror group's aims of winning sympathy from Muslims.