Nawazuddin Siddiqui is celebrated as one of Indian cinema's most versatile actors, often drawing comparisons to the late Irrfan Khan. His commitment to portraying complex characters with depth and authenticity is evident in his role as Ramanna, a serial killer, in Anurag Kashyap's 2016 neo-noir psychological thriller, Raman Raghav 2.0.

Siddiqui recently reflected on the challenges and impact of this role, stating, "When I got that role, I knew it wouldn't be easy. It wasn't the kind of role you could just show up and perform casually. It demanded serious mental and emotional preparation". He acknowledged the difficulty of embodying a character so removed from his own personality. To prepare, Siddiqui isolated himself in Lonavala for 5-6 days to internalize the character's disturbing mindset. He focused on believing Ramanna's chilling perspective: "I eat, drink, sleep, and kill. It doesn't matter to me. I don't even feel pain. You kill with the justification of humanity or religion—I kill just because".

This intense immersion took a physical and psychological toll on Siddiqui. "This role was so psychologically complex that it affected me physically too," he explained. During filming, he became seriously ill and was hospitalized, where he was reportedly found repeating Raman Raghav's dialogues while unconscious. "After 8–10 days, I recovered and returned to finish the film. But that experience… it never really left me". He described the shoot as a "mentally draining" experience.

Raman Raghav 2.0 is a cat-and-mouse chase between Ramanna (Siddiqui) and a corrupt cop, Raghavan, played by Vicky Kaushal. The film, inspired by a real-life serial killer from the 1960s, is divided into eight chapters. Kashyap initially wanted to set the film in the 1960s but opted for a contemporary setting after his previous period film, Bombay Velvet, failed commercially.

Siddiqui's dedication to the role involved extensive research, including watching YouTube videos and studying the behavior of psychopaths. He also spent time alone to contemplate the character. One particularly challenging scene involved a 10-minute monologue, which Siddiqui had to deliver repeatedly from different angles, resulting in him speaking for 300 minutes straight.

Despite the difficulties, Siddiqui felt confident in taking on the role because of his trust in director Anurag Kashyap. The two have collaborated on several projects, including Black Friday and Gangs of Wasseypur. Siddiqui appreciates Kashyap's ability to bring out the best in him.

Raman Raghav 2.0 premiered at the Cannes Film Festival's Directors' Fortnight section and received critical acclaim. Critics praised Siddiqui's performance as chilling, unnerving, and convincing. Some noted that while the film itself had flaws, Siddiqui's portrayal of Ramanna elevated the movie.

Namrata Joshi of The Hindu called Raman Raghav 2.0 a "taut thriller". Anna M.M. Vetticad lauded Siddiqui's "eerie, scary, [and] disgusting" performance and his ability to elicit laughs through his character's matter-of-fact approach to murder. Mohar Basu of The Times of India found the film crude and suspenseful, though difficult to watch due to its unsettling nature.

While Raman Raghav 2.0 is not a biographical depiction of the real serial killer, it explores the complexities of the human psyche and the dark underbelly of Mumbai. Siddiqui's portrayal of Ramanna remains one of his most memorable and challenging roles, demonstrating his commitment to his craft and his willingness to explore the depths of human darkness.