A journalism graduate of the University of the Philippines Baguio, Aquino began her career as a model, before making her film debut with a minor role in the action drama Mumbaki (1996).

Aquino established herself as a leading actress playing villainous parts in the drama series Magkaribal (2010), Maria la del Barrio (2011), Apoy sa Dagat (2013), And I Love You So (2015), Till I Met You (2016), and Dirty Linen (2023).

Among her notable performances are a widowed mother in the horror drama Amorosa (2012), a military intelligence officer in the action series Ang Probinsyano (2017), and a middle-aged woman smitten by a younger man in the erotic comedy Glorious (2018).

Described by various media publications as among the most beautiful and finest Filipino actresses of her generation, Aquino has been involved in charitable work and causes, including education, gender equality, and women's rights.

[15] Nestor Torre Jr. of the Philippine Daily Inquirer described her portrayal as "merely serviceable", but believed the antagonistic character changed people's perception of her, as she had previously played "sweet-and-lovely roles".

[14] Chito S. Roño cast Aquino as a woman who begins a sexual relationship with her godson in the erotic drama Laro sa Baga (2000), the script of which she found risky but necessary for artistic growth.

[20] The critic Andrew Paredes of the Manila Standard termed it a "rare local film that stands taller than a Hollywood release" and commended Aquino's "wonderful, understated performance".

[22] In February 2002, Aquino made her stage debut in a Folk Arts Theater production of Eve Ensler's play The Vagina Monologues, portraying a Bosnian woman subjected to rape.

[23] Following her theater appearance, Aquino featured in Mark Meily's critically acclaimed independent comedy-drama Crying Ladies, co-starring Sharon Cuneta and Hilda Koronel,[24][25] playing a professional mourner who has an affair with her friend's husband.

[27][28] Eddie Cockrell from Variety called the film a "vigorous, ambitious, big-hearted comic meller" and credited the ensemble for "comfortabl[y] navigating between broad comedy and legitimate pathos".

[35] In ICU Bed Number 7, an adaptation of the Palanca Award-winning screenplay from writer-director Rica Arevalo, she took on the role of a daughter conflicted with ending the life of her father (played by Eddie Garcia) with terminal illness.

The film tells the story of a woman suffering from breast cancer who returns to her hometown and finds companionship with a local whale shark spotter (played by Lucero).

[41] In preparation, she spent time with cancer support groups; and to get into her character's physical and mental space during filming, wore a chest binder and cut her hair short.

[46] Aquino next starred alongside Cherry Pie Picache and Juliana Palermo in Brillante Mendoza's drama Summer Heat (2006), about a dysfunctional family with a controlling patriarch (played by Johnny Delgado).

[52] In 2007, Aquino portrayed a woman sending anonymous letters to Christopher de Leon's character in Eddie Romero's final directorial effort, Faces of Love (2007),[53][54] which premiered at the 2007 Cinemalaya Independent Film Festival.

[63][64] To avoid being typecast in roles of martyred wives, Aquino accepted the offer to star as Vera Cruz, a prominent fashion designer and main antagonist, in the revenge drama series Magkaribal (2010).

[65] Her performance received generally positive reviews,[67] with Ricky Lo of The Philippine Star finding Aquino to have "reaffirmed her thespian chops": "Watching Vera Cruz is like riding a roller-coaster of powerful emotions.

[80] Earl Villanueva of the Philippine Entertainment Portal was enthusiastic about the film's "bold, shocking" production and described Aquino as a stand out: in his opinion, she conveyed a credible quality that her role required.

[97] Writing for the Philippine Entertainment Portal, Jocelyn Valle criticized Aquino's lack of stage technique: "[She] look[ed] uneasy and tentative, thus compromising what could've been effective and felt performances.

[99] She began 2014 by appearing in Ikaw Lamang, a period drama series set in a fictional plantation in 1960s Bacolod,[100] in which she played Rebecca Marivelez, a submissive and unhappy wife of a politician.

[108] The critic Maridol Ranoa-Bismark described the show as conventional, but praised Aquino's portrayal, writing that she "shifts from pathetic to furious and back with such passion, you want to let her carry you away in her torrent of emotions again and again".

[119] Aquino was reluctant to accept the film producer Deo Endrinal's offer to star in the 2018 erotic romance Glorious, but agreed after the director Connie Macatuno convinced her to take the role.

[122] Jill Tan Radovan of the Philippine Entertainment Portal wrote: "[Aquino] can easily take on challenging roles ... apart from her obvious acting talent, she has the grace and bearing required".

[133] Under Dreamscape Entertainment, Aquino portrayed a villainous fashion designer in the drama series Fit Check: Confessions of an Ukay Queen, which premiered on Amazon Prime Video on July 6, 2023.

[137][138] "One of her biggest strengths is her versatility", wrote ABS-CBNnews.com critic Liezel dela Cruz, "which allows her to play pretty much any character in any genre ... far different from her other recent portrayals, proving time and again that she can do it all".

[144] In 2006, Amy Cortez of The Manila Times observed that early in her career, Aquino had a preference for "meatier roles from independent filmmakers rather than take on insignificant offers from mainstream producers".

[65] Fiel Estrella of CNN Philippines wrote that her antagonistic roles are "something she can pull off with her signature grace and the right amount of unexpected menace", and identified a theme of characters that embody "humanity, redemption, [and] goodness".

[152] Her Ang Huling Cha-Cha ni Anita director Sigrid Andrea Bernardo recalled that Aquino was "humble and treats her fellow actors with utmost respect", and has identified a willingness in "redefining her screen persona" by detaching herself "from her usual mainstream roles".

[168] According to the online portal Box Office Mojo and the review aggregate site Rotten Tomatoes, Aquino's most critically and commercially successful films include Lea's Story, Crying Ladies, Siquijor: Mystic Island, Amorosa, Captive, and On the Job.

[169][170] Her television projects include the primetime series Magkaribal,[65] Maria la del Barrio,[72] Apoy Sa Dagat,[88] Honesto,[99] Ikaw Lamang,[100] Bagito,[105] And I Love You So,[107] Till I Met You,[114] Ang Probinsyano,[116] and Dirty Linen.