He quickly established a strong reputation for his work with optical networks and security protocols: specifically, lightwave networks, with the goal of developing novel architectures, protocols and algorithms for the next generation of high-speed networks designed to exploit wavelength-division multiplexing (WDM) optical technology; network intrusion detection, with the goal of detecting network software vulnerabilities and attacks in real time; and wireless and sensor networks. Mukherjee became renowned for his knowledge in these areas, and has become a popular speaker at optical networking conferences throughout the world. He recently served as general co-chair of the 2011 Optical Fibers Communication Conference, held in Los Angeles, and gave keynote/plenary talks at similar conferences held in Cartagena, Spain, and Stockholm, Sweden.

He also has been a prolific author during his quarter-century at UC Davis, with a staggering list of published articles and research papers to his credit. His graduate-level textbook, 2006's Optical WDM Networks, remains an invaluable resource to this day; the 956-page book is part of Springer's Optical Networks series, which Mukherjee edits. He also serves — or has served — on the editorial boards of eight journals, including IEEE/ACM Transactions on Networking and IEEE Network. He was made an IEEE Fellow in 2006.