At least 18 ISIS members, including 10 suicide bombers who used vehicle-borne improvised explosive devices (VBIEDs), attacked forces loyal to the Syrian regime in the city, the Syrian Observatory for Human Rights reported.
The UK-based monitor reported at least 25 Syrian and pro-Syrian regime militia members were killed. It added that five Iraqi militias were involved.
"It's the biggest attack on al-Boukamal since they lost it" in November 2017, said Rami Abdel Rahman, the head of the Observatory.
"ISIS now controls several parts of the city. Fighting is ongoing in the center," he added.
The Observatory said the death toll on all sides in the 18-day operation has reached about 300.
Syria's state-run media, SANA, made no mention of the attacks at the time of publication.
Al-Boukamal is in the Middle Euphrates River Valley about 440 kilometers east of Damascus.
US Defense Secretary James Mattis has called the area ISIS's "last stand."
The Iraqi army, Sunni tribal fighters and Shiite-led Hashd al-Shaabi paramilitias announced in November 2017 they captured al-Qaim, an Iraqi border crossing that links to al-Boukamal. That operation was supported by the US-led Global Coalition to Defeat ISIS.
Hashd media reported that Iraq's commander of operations in western Anbar, Qassim Musleh, met Hashd's local commander Rashid Fleih, to discuss joint coordination and patrols on Thursday. Anbar is heavily Sunni, while the Hashd are Shiite-led.
Northwest of al-Boukamal in southern al-Hasaka governorate, the Syrian Democratic Forces (SDF) announced on Thursday they have advanced 7.5 kilometers toward the ISIS strong hold of Dashisha.
The group, spearheaded by the People's Protection Units (YPG), said they liberated the villages of al-Marjan, Qalib Tahtani, al-Khawira, and seven nearby farms.
SDF announced 46 ISIS fighters, including four emirs, were killed. SDF put its own casualties at two wounded.
The SDF is the partnered ground force of the coalition. The Iraqi Air Force and ground forces have provided air support for Phase 2 of Operation Roundup.
On the Iraq-Syria-Jordan border, the coalition announced on Friday that "coalition trained and backed partner forces killed seven Daesh terrorists" during counter-ISIS patrols within the 55-kilometer de-confliction zone near at-Tanf.
"At least one Daesh member self-detonated his suicide vest during the ensuing exchange of fire. Seven Daesh terrorists were killed and there were no Coalition or partner casualties," read the coalition statement.
The coalition trains local tribal forces at the base.
"This is another example of the dedication and hard work by our partners to defeat the remaining Daesh threat in southern Syria," said Maj. Gen. Felix Gedney, the coalition's deputy commander for strategy and support. "To take the fight to Daesh and deny them safe haven has been our primary focus. If we are to attain stability in the region, we must carry on our committed effort to achieve a lasting defeat of Daesh here."
