The plot revolves around young lovers Lyka Raymundo (played by Angel Locsin) and Noah Ortega (played by Piolo Pascual). Lyka is a young woman aspiring to be a fashion designer, working as a fashion assistant in the House of Elle. She lives with her aunt Clara and her step cousin Anton.

Noah is the adopted son of General Leon Cristobal, who took over guardianship of Noah after his real father, Emil Ortega, died in a tragic accident involving an unknown wolf. Noah is a second lieutenant of the Philippine Army, being actively recruited to join the Luna force, an elite team specializing in protecting humans from dangerous werewolves and vampires.

Lyka’s position as fashion assistant to Lady Elle is foreshadowed by the fact that she is a werewolf who hasn’t transformed yet, who doesn’t know she is one because her werewolf mother abandoned her as a child. Her mother is Vanessa Blancaflor Raymundo, daughter of Lorenzo Blancaflor, the twin brother of Eleanor Blancaflor (played by Pilar Pilapil), owner of the fashion house icon, House of Elle. Secretly, the Blancaflors are a powerful werewolf clan who led the Waya Council for generations. Destiny brought Lyka to the seat of the Wayas.

Lyka is believed to be the last hope, the “Huling Bantay” (“Last hope/Last Guardian”) of her fellow Werewolves. Lady Elle instantly sensed her presence at a chance encounter, and immediately hired Lyka to work directly with her team so she could closely watch over her and help her through her transformation, which she believed would occur sometime or after her 21st birthday.

At about the same time when Lyka applied at the House of Elle, the Wayas had been searching for their Huling Bantay who would have the strength and power to save the werewolf population from the deadly rays of the upcoming Red Moon (“Pulang Buwan”), a phenomenon that occurred every 500 years, which could potentially purge and destroy all the werewolves. Only the Last Guardian, the strongest Waya, could save the species by “raising the stone of Remus”. The last “Huling Bantay” was Remus, who kept the talisman for the next Guardian to use. Lady Elle was certain that Lyka was worthy and strong enough to be their Last Guardian.

In the House of Elle, Lyka crosses paths with Noah, Lady Elle’s bodyguard and driver. Lyka and Noah fall in love, but their relationship is hindered by Noah’s deep hatred for werewolves, as he blamed them for killing his father and foster father. By the time they had fallen deeply in love, Lyka had reached her “time” – fully accepting her werewolf nature and the bigger responsibility as the Last Guardian. Despite the many obstacles, Noah and Lyka’s love for each other prevailed. They marry, and together battle and defeat their enemies.

Three other characters create additional conflict: Noah’s friend, Gabrielle Dizon (played by Shaina Magdayao), a deep penetration agent tasked to bring Noah over to the Luna Force for the sinister purposes to destroy and rid the country of all werewolves altogether, complicated by the fact that she was in love with Noah and truly cared for him; Anton Rivero, Lyka’s step cousin, her protector against his abusive step mother Clara, and obsessively in love with Lyka; and General Silva, a secret rogue werewolf banished by the Wayas, out to seek revenge and destroy the Council.

There are two opposing groups in the story—the Lunas and the Wayas. The Lunas were organized by the Philippine Army to protect humans against werewolves and vampires, but a small faction led by General Silva, held a personal grudge against the werewolves, aiming to undermine Luna leadership and destroy the entire werewolf population. Silva had a special interest in Noah, who was recruited not only for his superior skills, but mainly because flowing through his blood was a natural immunity to werewolf bites, a gene inherited from his father. General Silva, together with Anton, manipulated Noah to join the force to obtain his blood and develop an antidote for the poisonous werewolf bites.

The other opposing group, the Waya Inc. was led by Lady Elle. Wayas controlled and presided over the affairs of the white werewolves and executed justice over the black werewolves and vampires who preyed on humans. Since the vampires had retreated into hiding, the Waya mostly had to deal with the rogue werewolves, secretly working with the Lunas to provide protection for their species.

At that time, there were two warring factions among the werewolves that threatened the agreement between the Wayas and the Lunas and disturbed the peace within the population. While the white werewolves respected the human beings in their midst and lived in peace with them, albeit secretly; the black werewolves killed humans, the biggest reason why werewolves were feared. The Wayas controlled and led their species, and imposed justice on werewolves who drank human blood, doing their best to apprehend and kill the black werewolves.

On the night of the Red Moon, Lyka, who had fully accepted her role as “Huling Bantay”, successfully retrieved the Stone of Remus, narrowly lost her life, and saved her people from the purge. She exhorts them to co-exist harmoniously with human beings, and to stop the prejudice against the black wolves. She became their Head Guardian, leading the council for an integrated black and white werewolf population.

Lyka later defeats the bigger threat of her stepcousin’s metamorphosis into a demon werewolf. Anton was an accomplished chemist, whose specialty was animal diseases and virus mutations. All his life, he worked towards finding a cure for his werewolf nature, believing that he was infected and did not have an inherited gene. As a child, he was accidentally bitten by Vanessa, then in werewolf form. Picked by General Silva to work on the antidote for poisonous werewolf bites, Anton discovered a more potent formulation, a mixture of Lyka’s and Noah’s blood which he injected into his system, gave him an immunity to werewolf bites, and the ability to heal his wounds quickly. Using the Stone of Remus which he stole from Lyka, and following instructions from an ancient book General Silva had, he was transformed into a powerful werewolf. Unfortunately, his distorted love and obsession for Lyka changed his soul and personality, turned him into a formidable enemy, who almost defeated Lyka and Noah in their last battle.

Celebrating their victory, and the peaceful coexistence of humans and werewolves, Lady Elle toasts the pregnancy of Lyka and Noah, showing another foreshadowing of the two sequels, Imortal and La Luna Sangre. Lyka and Noah are pushing two strollers, indicating they will have twins.