Hairi (Saiful Apek) is a loser who lives in Metrofulus. While working in the lab, he accidentally drinks coffee that has been contaminated by a virus-infected gecko. He soon finds himself doing the most insane things, such as sticking to walls, making chirping cicak noises and adding bugs to his menu. He turns to his best friend and apartment mate, Danny (Yusry Abdul Halim), and begs him to find the reason behind his strange antics. Meanwhile, the people of Metrofulus are constantly being infected by new strains of viruses, and the only cure seems to come only from Professor Klon's (Aznil Nawawi) lab. Suspecting something amiss, Hairi and Danny launch their own investigation and discover that Professor Klon is not only the creator of such viruses, but also has a more sinister plan up his sleeve, backed by his business partners, the Ginger Boys Ramlie and AC Mizal, who first tend to take revenge on Professor Klon's failed experiment on them; making their senses turn abnormal.

The evil Professor Klon is back… This time, not only to overthrow the Government and become the President of Metrofulus, but also to control the world’s supply of fresh water through his ingenious plan, “Black Water”. When our blue planet has only 72 hours before turning black, Cicakman comes to the rescue. But much to his surprise he faces his old enemies, Ginger Boys, who return even more powerful in a spiritual form… as Ginger Ghosts. In addition he is now faced with Professor Klon’s hired assassin, Rrama… an assassin who derives pleasure in killing as if it were a pure art form.

Set after 7 years of the event of Cicakman 2: Planet Hitam. Metrofulus superhero, Cicakman had disappeared, many people say Cicakman is dead or retire. So, The new superhero has emerged known as Superbro has become a major superhero in Metrofulus and he is venerated by many people. The man named Man (Zizan Razak) has found a box left by former Cicakman (Saiful Apek) at the Cicakman monument