In 2001, she staged her first major solo concert Lani Misalucha: The Crossover Live Tour at the Araneta Coliseum,[4] earning an Entertainer of the Year win at the 2002 Aliw Awards.

[5] Her vocal performances have earned praises from musical artists such as Dionne Warwick, Joe Jackson, Gladys Night, James Ingram and Whitney Houston.

Misalucha sang the song "Ang Iibigin ay Ikaw" (written by Jimmy Borja) which was a finalist at the Metro Manila Popular Music Festival and later received the Awit Award for Record of the Year.

Misalucha's interpretation of "Can't Stop Loving You" (written by Dodjie Simon) won her songwriter the Grand Prize at the 1999 Metropop Song Festival.

The album also included songs written by some of the Philippines' contemporary composers such as Vehnee Saturno ("Ang Lahat Ng Ito Ay Para Sa Iyo"), Jimmy Borja ("Bukas Na Lang Kita Mamahalin") and Trina Belamide ("Save This Heart").

Her first major solo concert in September 2001 at the Araneta Coliseum entitled, "Lani Misalucha, The Crossover Live Tour" and was repeated at the Cultural Center of Philippines.

Misalucha became the first Asian to headline in a Main Showroom of the Las Vegas Strip,[11] performing with Hawaii's premiere showband Society of Seven at the Jubilee Theatre of Bally's Hotel and Casino.

[12] Just as the album turned Gold and Platinum in 2007, Lani came home to regale her Filipino audience with songs and stories in a one-night engagement at the Araneta Coliseum on March 17, 2007.

The concert, aptly titled, Missing You, was packed by almost 18,000 fans and followers, a testament not only to Lani's rousing world-class talent, but also to her dedication to the people who have come to love her music.

With her successful 15-month run at the Bally's, a series of road tours, and subsequent offers to headline shows in the entertainment capital of the world, Asia's Nightingale sky-rocketed to world-wide recognition as the new Siren of the Strip.

Misalucha was the voice behind the version of Gary Valenciano's "Natutulog Ba Ang Diyos?," theme song of the ABS-CBN television soap opera that goes by the same title.

Breaking ground on another stage yet again, Lani made history, in October 2011, when she debuted as lead host of the first mainstream travel and lifestyle television show featuring Las Vegas.

'It's Vegas with Lani' has for its first season, thirteen (13) 30-minute episodes that offer a new perspective of Sin City, featuring restaurants, shops, destinations and adventure tours for both local and global audiences.

From her serendipitous debut to her recognition as an artist of international caliber, the story of Lani's journey with music transcends every song, heartfelt and genuine in its delivery of all the best that is yet to come.

[16][17] In a 2001 interview with journalist Ricky Lo, she revealed that her most favorite Streisand song is "As If We Never Said Goodbye" and Houston's "Saying All My Love for You, " which she used as her piece in a number of amateur singing competitions.

[20] Bobby Yalong of Asian Journal praised her vocal power, pitch and melismatic style during her concert at The Town Hall in New York City saying: "There's longevity in her voice, consistency and purity of tone, clear resonance, and excellent projection.

"[31] Jonathan Chua of The Philippine Star also praised her vocal performance during her concert at the Cultural Center in 2001 saying: "a remarkable instrument, strong without being strident, high without being shrill.

[33][34] A significant figure in Philippine pop music, she has been cited and acknowledged by numerous artists as an influence and inspiration including Morissette,[35] Zephanie Dimaranan,[36] Stephanie Reese,[37] Jade Riccio,[38] Marielle Corpus,[39] and Ramiele Malubay.

[40] Her music has also been recorded and performed by a variety of artists such as Jake Zyrus,[41] Julie Ann San Jose,[42] Angeline Quinto,[43] Klarisse de Guzman,[44] Jed Madela,[45] and Sarah Geronimo.

Misalucha has also been credited for her work and performances with international artists such as Andrea Bocelli,[56] Brian McKnight,[57][58] Josh Groban,[59] Stephen Bishop,[60] Sergio Mendes,[61] Kenny Loggins[60] and Jim Brickman.

[66] She has been dubbed as the "Siren of the Strip"[67] for the successes of her concert residencies in Las Vegas, earning her special recognitions from former Governor of Nevada Kenny Guinn and former Mayor of Los Angeles James Hahn.

[68] Moreover, two former Mayors Oscar Goodman (Las Vegas) and Willie Brown (Los Angeles) proclaimed December 4 and August 17 as the "Lani Misalucha Day" in their respective cities.

[71] In 2015, she donated the proceeds of her concert at The Town Hall in New York City to ABS-CBN's Bantay Bata Foundation and Filipino-American Community Development Center of Ocean County, Inc (FCDC).

Misalucha later worked the lounge circuits as a soloist and lent her voice to numerous commercial jingles and karaoke tapes, thus earning her the epithet, "Multiplex Queen.