Tatiana Santo Domingo was born on 24 November 1983 in New York and raised in Geneva, Switzerland, and Paris, France. Her Father Julio Mario Santo Domingo, Jr. (1958–2009) was the son of Julio Mario Santo Domingo (1923–2011), who was cited as the second richest man in Colombia by Forbes in 2011. Her grandfather was owner of the Santo Domingo Group and the Colombian Bavaria Brewery, which was one of the largest breweries in South America. When he died in 2011, he left a sixth of his wealth to Tatiana Santo Domingo.

According to one source, Santo Domingo attended the International School of Geneva and then enrolled at a boarding school in Fontainebleau, near Paris, where she met her Future husband Andrea Casiraghi. However, according to Bob Colacello in a special spread for Vanity Fair entitled, "Fortune's Children," she actually attended Institut Le Rosey and École Jeannine Manuel. Colacello also claimed that she holds a Bachelor of Fine Arts from American University in London. She earned her BFA in 2005.

Santo Domingo supports several charity organizations, most notably the Motrice Foundation, which funds research into cerebral palsy and which her husband Andrea Casiraghi also supports. In August 2006 she and Casiraghi paid a visit to Manila on behalf of a joint venture of the World Association of Children's Friends and the Virlanie Foundation.

In 2010, Tatiana Santo Domingo renounced to her US citizenship, according to the Internal Revenue Service.

In 2011, Santo Domingo partnered with Dana Alikhani, daughter of the late Hossein Alikhani, to launch Muzungu Sisters, which focuses on ethical Business practices that allow them support local artisans, buy handmade garments at a fair price and then sell them. Their brand has been supported by other socialites, such as Eugenie Niarchos, Margherita Missoni and Gaia Repossi.

In July 2012, Princess Caroline released a statement announcing that Andrea Casiraghi and Tatiana Santo Domingo became engaged after a seven-year relationship. Prior to their wedding, she had already accompanied Casiraghi at some of most important social events in Monaco, such as the Rose Ball, the enthronement of Prince Albert II, the Monaco Grand Prix and the wedding of Prince Albert and Charlene Wittstock.

On 6 November, Santo Domingo announced to La Voz Libre that she was expecting a baby. She gave birth to a boy, a son named Alex Andre Andrea Stefano "Sasha" Casiraghi, on 21 March 2013, in London, England. As his parents were not married at the time of birth, he was not then included in the Monegasque line of succession. However, due to their subsequent marriage their son currently occupies the fifth position in the line of succession to the Monegasque throne.

Casiraghi and Santo Domingo were married in a civil ceremony in the Princely Palace of Monaco on August 31, 2013. A religious ceremony was later held in Gstaad, Switzerland, on February 1, 2014. Their second child, India Casiraghi, was born in London on 12 April 2015. She currently occupies the sixth position in the line of succession to the Monegasque throne.

Santo Domingo is known for her unique fashion sense, which varies from an elegant style to a vintage, boho-chic, hippie one. She cites Loulou de la Falaise as her style idol. She is fluent in Spanish, French, English, Portuguese and Italian. She is close friends with socialites such as Charlotte Casiraghi, Eugenie Niarchos, Gaia Repossi, Dana Alikhani, and Teresa and Margherita Missoni.. In December 2017, a Vogue magazine article confirmed she is expecting her third child.