The grenade attack was the 11th in the city since January.
Inspector Roger Legaspi, chief of police precinct II, said auditor Maximo Pamilian, 54, and his son, Junie, died from multiple shrapnel wounds.
Pamilians three other children Janisa, 18; Basron, 22; and Mican, 17 were wounded in the blast.
Investigation showed that an unidentified man casually approached the frontyard of the Pamilians and hurled the grenade into an open window.
Legaspi said probers are convinced that the attack was "work-related."
The ARMMs DepEd office has been the subject of controversies lately due to alleged fund anomalies and non-payment of benefits to hundreds of teachers in the region.
The grenade attack came less than a week after hundreds of teachers staged a rally in front of the office of ARMM Vice Gov. Mahid Mutilan, the regions concurrent education secretary, to protest the long-delayed remittance of their monthly contributions to the Government Service Insurance System.
A month ago, motorcycle-riding men gunned down Richard Lanzaderas, finance chief of the ARMMs Department of Environment and Natural Resources, along a busy street here.