Her starring roles in Impostora (2007), All About Eve (2009), Beauty Queen (2010), Hawak Kamay (2014), A Love to Last (2017) and Ang sa Iyo Ay Akin (2020) established her as a leading actress in soap operas.

She also received widespread critical acclaim for her performances in Dukot (2009), Mga Mumunting Lihim (2012), Haunted Mansion (2015), Bliss (2017) and Culion (2019).

[5] Her performance landed Calzado her first lead role in the romantic drama Te Amo, Maging Sino Ka Man opposite Argentine actor Segundo Cernadas.

Her performance was lauded by the critics, earning Calzado her first Gawad Urian Award for Beat Supporting Actress, in addition to a nomination at the Metro Manila Film Festival in the same category.

[10] A surprise hit at the box office, it was followed up by another romantic drama Eternity with Dantes which also stars Jennylyn Mercado and Mark Herras.

The series was still a success, becoming the third most watched program with an average rating of 32.2%, based on Mega Manila TV household between January and February 2006.

[20] Calzado also starred in the supernatural horror Ouija with Judy Ann Santos, Jolina Magdangal and Rhian Ramos.

She starred in the romantic drama Batanes: Sa Dulo ng Walang Hanggan with Taiwanese actor Ken Chu.

[48] She next played the Black Lady in Topel Lee's supernatural horror White House alongside Gabby Concepcion, Lovi Poe and Maricar Reyes.

"[50] In 2011, Calzado replaced Regine Velasquez as the lead in the latter part of the romantic comedy I Heart You, Pare!, which also stars Dingdong Dantes.

[54] She became an occasional performer in the musical variety show ASAP and starred in Wenn V. Deramas' romantic drama the Kahit Puso’y Masugatan with Gabby Concepcion, Jake Cuenca and Andi Eigenmann.

She starred in Chito S. Roño's romantic drama Etiquette for Mistresses, co-starring Kris Aquino, Claudine Barretto, Kim Chiu and Cheena Crab.

"[66] Rito Asilo of Entertainment Inquirer also praised her portrayal saying: "she proves that a fine performance isn’t compromised by the quantity of scenes she appears in.

[75] Calzado made her television comeback in 2017 through the family drama A Love to Last, co-starring Bea Alonzo and Ian Veneracion.

[80] For her portrayal, she received a nomination for Best Actress at the Cinemalaya Philippine Independent Film Festival and PMPC Star Awards for Movies.

For ger performance, Calzado received a nomination for Best Drama Supporting Actress at the PMPC Star Awards for Television.

She reunited with Sunshine Dizon, Karylle and Diana Zubiri in Mark Reyes' Mystified, a fantasy film which premiered on the streaming service iflix.

[85] She next starred in the crime drama Pandanggo sa Hukay, an entry to the Cinemalaya Philippine Independent Film Festival.

[88] In 2020, Calzado starred as the main antagonist in FM Reyes' Ang sa Iyo ay Akin, co-starring Jodi Sta.

[99] She is one of the co-founders of She Talks Asia, a non-profit organization which centers in "raising awareness of the importance of physical, emotional and mental well-being.

[102] In 2009, she also celebrated her 27th birthday with the beneficiaries of Gawad Kalinga Community Development Foundation, Inc.[103] Calzado is also one of the board of directors of the SEC-registered nonprofit and nonstock organization League of Filipino Actors which is "composed of the showbiz industry’s co-creators and collaborators in order to give them a collective voice on different issues.

"[104] In 2016, Calzado was appointed as one of the national female ambassadors of the World Wide Fund for Nature which "help spread WWF’s solutions on climate change, conservation, resource protection and environmental education.

Francis Joseph Cruz from Rappler praised her portrayal saying: "She is the heart of the film, the passive sufferer who can't do anything but absorb the pain and pleasure.

"[116] Filipino director Adolf Alix Jr. praised Calzado's performance in the film Batanes: Sa Dulo ng Walang Hanggan, saying: "I think her willingness to experiment and take unconventional roles make her stand out.

Ryan Oquiza from Rappler called her as the one who stole the show saying that she "embodies the bravado of Anjanette Abayari and the gravitas of Angel Locsin.

"[124] Mike Diez from The Philippine Star praised her performance saying: "She brings weight to the character and exudes an aura of authority.

"[125] The Swiss luxury watches and jewelry brand, Charriol, introduced the "Izadore bangle", named after her as part of the International Women's Month celebration.

Starting Over Again previously held the record as the highest-grossing Filipino movie at the global box office until it was surpassed by A Second Chance in December 2015.

[138] In 2012, Calzado, along with Judy Ann Santos, Janice de Belen & Agot Isidro, received two major awards at the Cinemalaya Independent Film Festival.

[145] For the film Mystified (2019), which was produced by Sanggre Productions Inc, co-founded by Calzado with Sunshine Dizon, Karylle and Diana Zubiri, won Best Single Drama or Telemovie at the Asian Television Awards.