As a lawyer, he was named the district attorney of San Isidro, Nueva Ecija in 1900 and later as fiscal of the provinces of Bulacan and Bataan.

[6] Rafael Palma (1930) noted that during his college years, his collecting instinct was already evident when he dedicated himself to gathering plants and flowers in Nueva Ecija, where he also sought the company of and spent time with rural communities.

As a young law student, his interest in Spanish literature developed through readings of Juan Valera's novel entitled "Pepita Jimenez" and other available works.

[9][7] His home in Intramuros became a meeting place for literary figures including Cecilio Apóstol (Catulo), Fernando María Guerrero (Fulvio Gil), José Palma, Rafael Palma, Jaime C. de Veyra, Macario Pineda, Mariano V. del Rosario, Salvador V. del Rosario, Ysidro Paredes, Macario Adriatico, Jose Clemente Zulueta and Jose G.

[citation needed] His brother, Escolastico, became a pianist for silent films and contributed as a poet and realist story teller to Philippine magazines and newspapers.

[citation needed] He has two lines of descendants with four children with his first wife Ursula Paez: Jose, Rosario, Escolastico and Antonio; and eight children with his second wife Margarita Torralba: Leticia, Fernando, Socrates, Federico, Hipatia Patria, Espacia Lydia, Glicera Ruth & Margarita.

Epifanio was a young associate editor of the revolutionary paper "La Independencia" (1898), writing in prose under the pen name G. Solon and also a member of the Malolos Congress.

He amassed a collection of nearly 200 paintings and sculptures, musical literature, opera records, printed materials, documents and manuscripts related to the revolution and historical pictures.

[16] There is an anecdote about de los Santos and Clemente Jose Zulueta having a disagreement, with Antonio Luna offering his guitar to whoever won the argument.

[17] Epifanio de los Santos was elected to the Malolos Congress in September 1898, serving as one of three representatives from Nueva Ecija until November 1899.

[2] As director of the Philippine Library, he reportedly dedicated himself to his work, giving up "all his other avocations except music and bibliophily," according to Gabriel Bernardo.

[3] Several schools, streets, a college, a hospital, a printing press and an auditorium in the National Library of the Philippines are also named in his honor.