Castro rose to the moment in 2009 and led a massive protest movement, honing her public persona in speeches to her loyal supporters.
Although the movement could not reinstate her husband as president, it created the Liberty and Refoundation (Libre) party, which has now put her within reach of the presidency.
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Xiomara Castro Leads Polls in Honduran Presidential Election
A favorite in the polls, she may be able to end the two-party rule in Honduras, governed by the National Party and the Liberal Party for over 100 years.
In 2013, Castro, who would also become the first woman to be president of Honduras, lost her first presidential bid against incumbent Juan Orlando Hernandez of the National Party.
"I believe firmly that the democratic socialism I propose is the solution to pull Honduras out of the abyss we have been buried in by neo-liberalism, a narco-dictator and corruption," Castro said in a campaign speech, running on a platform well to the left of the Liberal Party candidate.
President Juan Orlando Hernandez (JOH) has faced accusations of involvement in drug trafficking, which he has repeatedly denied.
Castro, on the other hand, a promoter of "democratic socialism," wants to decriminalize abortion, reduce bank charges for remittances, create a U.N.-backed anti-corruption commission and repeal new laws that she says feeds corruption and drug trafficking.
When Zelaya was president, Castro was active in policymaking and pushed for social programs and subsidies for poor children, women and the elderly, which helped build her popularity.
The National Party, which has been beset by corruption scandals, has consistently red-baited Castro in order to remain in power.
"A vote for Xiomara is a vote for communism, socialism, chaos, hunger, violence, repression, abortion, poverty," went a National Party attack ad on television and social media.
Castro's party Libre is also part of the Sao Paolo Forum, an organization seeking to revive the Latin American left after the fall of the Berlin wall. Yet, many doubt Castro will adopt radical policies.
The reality is that "Honduras depends on trade with the United States and it's so weak it can't survive even a month of economic isolation from Washington," said political analyst Raul Pineda.