[5][6] Santa Maria wrote her first blog for The Huffington Post in March 2010 before joining the publication as its founding science correspondent and host of the Talk Nerdy to Me web series from October 2011 until April 2013.

Her parents, a school teacher and an engineer, both came from Catholic families and converted to Mormonism together as adults, raising their children in the religion, and for a while Santa Maria attended church daily before classes.

[16][better source needed] Her published research has spanned various topics, including clinical psychological assessment, the neuropsychology of blindness, neuronal cell culture techniques, and computational neurophysiology.

[16][better source needed] Santa Maria was enrolled in a doctoral program studying clinical neuropsychology at Queens College, CUNY, where she worked as an adjunct professor and laboratory researcher, but withdrew after a year of coursework to pursue science communication full-time.

[19]: Better source needed In 2009, Santa Maria moved to the Los Angeles area to begin a career in science communication, after previously having worked in academia.

[20][21] Santa Maria has appeared on various programs including Larry King Live,[13] Geraldo at Large (Fox News),[13] Parker Spitzer (CNN),[13] Studio 11, The Young Turks,[10] Attack of the Show!,[22] The War Room with Jennifer Granholm,[23] LatiNation,[24] and SoCal Connected.

New episodes premiere every Monday and guests typically revolve around those involved in STEM fields, however individuals with careers oriented in new media and pop culture also make appearances.

[35][3] Santa Maria wrote the foreword of atheism activist David Silverman's book, Fighting God: An Atheist Manifesto for a Religious World, published in December 2015.

[46] In a Point of Inquiry podcast interview, Santa Maria said that she takes antidepressants daily and that psychotherapy made a huge improvement in her mental health.