In the primaries, González Colón beat her opponent, former gubernatorial candidate Carlos I. Pesquera, 71% to 29%, securing the NPP's nomination for Resident Commissioner in the general elections.

[16] In 2024, Jenniffer González Colón for the third time entrusted Domenech[17][18] with the management of her primary campaign to become the NPP's candidate for governor in the November 5, 2024, general elections.

During his tenure as President of the PRYD's, Domenech led a team of 14 young Puerto Rican professionals in Central Florida that campaigned for several weeks for the Kerry/Edwards ticket.

Pedro Rosselló's gubernatorial campaign, both in island-wide political organizing, as well as platform and opposition research activities.

In November 2004, Domenech also organized and hosted YDA's Fall National meeting in San Juan, Puerto Rico.

[25] Following in the footsteps of many Democratic leaders, such as the young Hillary Clinton who registered Hispanics in Southwest Texas in the 70's, Domenech led voter registration drives aimed at potential Puerto Rican voters in Florida's I-4 Corridor in several election cycles between 2004 and 2010, staffed by YDA Puerto Rico chapter volunteers.

In December 2007, Domenech was appointed by Senator Hillary Clinton to Co-Chair her presidential campaign's Hillblazers, a national network of young professionals and students.

[35][36] The local legislative equivalent of the United States Congress' Congressional Research Service with a staff of about 120 and a budget of $10 million.

In early 2013, the Puerto Rico Supreme Court in Domenech Fernández v. Integration Corporate Services, et al[38] ruled unanimously in his favor in a case arising from a shareholders' dispute within the firm for which he had previously worked.

[39] In 2010 he founded and led until December 2024 Politank*, Corp.[40] a bipartisan government affairs firm in Puerto Rico which has represented Fortune 500 clients, and which hired Puerto Rico's former Secretary of State and Senate President Kenneth McClintock and at one point Guillermo San Antonio-Acha, former Legal Counsel to the Governor during Governor Aníbal Acevedo Vilá's administration and who served from late 2014 until early 2017 as the Popular Democratic Party of Puerto Rico (PPD) Electoral Commissioner.

It was an even more historical feat than his two prior victories led by Domenech, because in the 25 years of the Colegio Médico's existence, no one candidate had ever been elected three (3) times to its presidency.

[61] He is the great grandnephew of Manuel V. Domenech, an engineer, who was a member of the first Puerto Rico House of Representatives after the Spanish–American War of 1898, and was reelected in 1902 and 1904.

[62] Domenech is also second cousin of the former Commonwealth of Virginia's Secretary of Natural Resources,[63] Douglas Domenech who served in the Bush Administration as Deputy Chief of Staff for the United States Department of the Interior and who also served as Assistant Secretary for Insular Affairs of the United States Department of the Interior under the Trump Administration.