During the last quarter of the 17th century, Ilocos and Bulacan natives and Tagalogs from Cabanatuan migrated to Santo Domingo.

The Alejos, Juans, Samatras, Salamancas, Andreses, Pascuals and Tomases were the descendants of the founders of the town.

Santo Domingo is bordered by the municipalities of Talavera to the east, Quezon to the west, Science City of Muñoz to the north, Guimba to the northwest, and Aliaga to the south.

The 1896 St. Dominic Parish Church (Real St., Poblacion, Santo Domingo, 3133 Nueva Ecija)[13] belongs to the Roman Catholic Diocese of San Jose.

Ian Christopher D. Andal (Acting Parish Priest) (Vicariate of St. Dominic[14] - Diocesis Sancti Josephi in Insulis Philippinis, Suffragan of Lingayen-Dagupan; created: February 16, 1984, erected July 14, 1984, comprising the City of San Jose and the Science City of Muñoz and 12 other municipalities in Northern Nueva Ecija; Titular: St. Joseph the Worker, May 1).

[17] The St. Jerome Parish Church (Barangay Baloc, Santo Domingo, 3133 Nueva Ecija) belongs to the Roman Catholic Diocese of San Jose.

(since 15 May 2012) is the head of the Diocese (Vicariate of St. Dominic[14] - Diocesis Sancti Josephi in Insulis Philippinis, Suffragan of Lingayen-Dagupan; created: February 16, 1984, erected July 14, 1984, comprising the City of San Jose and the Science City of Muñoz and 12 other municipalities in Northern Nueva Ecija; Titular: St. Joseph the Worker, May 1).

The Iglesia Filipina Independiente, San Geronimo Church is also one of the landmark religious heritage of Santo Domingo.

Resty Valenzuela Ahyong Baloc established his own Dambana ni San Geronimo when he transferred from the Roman Catholic Church.

Poverty Incidence of Santo Domingo Source: Philippine Statistics Authority[18][19][20][21][22][23][24][25] As an agricultural town, Santo Domingo is famous for its scenic agricultural landscape amid its Philippine duck raising industry.