She received wider audience for her role as Sally, the main antagonist in the romantic drama Sa Dulo ng Walang Hanggan (2001).

Dizon also appeared in the romantic family drama Ploning (2008), where she received nominations for a Golden Screen and Gawad Pasado for Best Supporting Actress.

Dizon received critical acclaim for her role as an opulent woman diagnosed with cancer in the independent drama 100 (2008), for which she won a Luna and Gawad Urian for Best Actress.

Dizon's film appearances in the ensuing years including the action thriller 10,000 Hours (2013) and the epic war Heneral Luna (2015) have earned her nominations from major award-giving bodies in the Philippines.

After graduating from high school, she enrolled in De La Salle University, pursuing a bachelor's degree in communication arts.

[6] She made her screen debut in the teen series Gimik (1996) where she starred with an ensemble cast that included Judy Ann Santos, Marvin Agustin, Diether Ocampo, and G.

[12] In 2001, Dizon starred opposite Jomari Yllana in the war drama Gatas... Sa Dibdib ng Kaaway, which was the Philippine submission for Best Foreign Language Film at the 74th Academy Awards.

She played supporting roles in the action romantic Basta't Kasama Kita, the sitcom All Together Now, and her first series under GMA Network, Narito ang Puso Ko.

[21] For her performance, she won Best Actress at the Cinema One Originals Digital Film Festival and received nominations from Gawad Urian and Golden Screen Awards.

[25] She next starred with an ensemble cast as an evil werewolf and vampire-like creature in the tenth horror anthology Shake, Rattle & Roll X.

[27] Dizon received widespread acclaim for her performance, winning her first Best Actress trophies at the Luna, Cinemalaya Independent Film Festival and Gawad Urian, including nominations for a FAMAS and Star Awards for Movies.

[45] She also starred with an ensemble cast in the comedy Call Me Tita and the fantasy drama Sahaya, where Dizon played the character of a Badjao mother.

[46][47][48] She made her screen comeback in the romantic drama Belle Douleur opposite Kit Thompson, an official entry at the Cinemalaya Independent Film Festival.

Dizon starred with Carmina Villaroel in the horror Sunod and made a cameo appearance in the fantasy adventure Magikland, which were official entries at the Metro Manila Film Festival in 2019 and 2020 respectively.

[51][52] In 2020, Dizon starred alongside Nora Aunor and Kyline Alcantara in the drama Bilangin ang Bituin sa Langit.

[53] She continuously appeared in television productions in the next two years, playing secondary roles in Huwag Kang Mangamba (2021) as a feisty journalist, a strict parent in My Sunset Girl (2021) and as the main antagonist in Love in 40 Days (2022).

[61] Having appeared in numerous independent films and mainstream productions of varying genres since her career's inception in mid-1990s, she is noted for displaying depth and emotional connection to the characters she portrays.

[62] Edwin Sallan of Philippine Entertainment Portal described her portrayal in Belle Douleur (2019) as the best performance of her career, saying: "Mylene has mastered the art of nuanced acting that indie films are known for... [Her] subtle approach reminiscent of Hollywood actress Diane Lane (and equally as luminous) was effective in previous Cinemalaya entries such as Aparisyon (2012) and Mariquina (2014).

"[63] Writing for The Philippine Star, Tim Yap praised Dizon's ability to tackle any role she's given with strength, saying: "Even if her assigned characters are on the surface, weak, she gives it multiple dimensions.

[70] Media publications such as Spot.ph and Philippine Daily Inquirer have also included her on their list of notable Filipino villains, particularly for her portrayal as Sally Concepcion in the series Sa Dulo ng Walang Hanggan (2001).

[76][77] In late November 2021, Dizon participated in the launch of Mga Munting Babae, the Filipino translated version of Little Women by Louisa May Alcott, at the Performatura: Performance Literature Festival.