His practice heavily explores modern socio-political crises, drawing deep inspiration from television journalism, cinema, historical art, and digital media. By repurposing imagery found on the internet and print news, he crafts eerie, meaningful paintings that comment on pressing societal realities across India.

Santhosh's distinctive visual approach blends a unique representational style with carefully controlled color scales and sudden, quiet alterations in detail that challenge viewers. His highly acclaimed solo career launched in Mumbai in 2003 with his exhibition "One Hand Clapping/Siren." Since then, his provocative pieces have been showcased globally in major art capitals, including New York, London, Zurich, and Beijing. His contributions to the art world have earned him notable accolades, such as the Kerala Lalit Kala Academy State Award and the Kanoria Scholarship.