Entomopathogenic nematodes (EPNs) belonging to the genera Heterorhabditis and Steinernema are mutualistically associated with bacteria in the genera Photorhabdus and Xenorhabdus. The complexes of EPNs and their bacterial symbionts infect and kill a wide range of soil-dwelling insects that are harmful to crops. Given this advantage, these complexes have been primarily developed as a biocontrol agent to replace chemical pesticides on crops when society calls for healthy agriculture. This review examined recent advances in mutualistic bacteria of EPNs, secondary metabolites, and the mechanisms underpinning the interactions between mutualistic bacteria and insect hosts, as well as their potential application as a biocontrol agent. Based on this, new insights were provided to address the current issues that restrict the exploration of such biological agents, informing future research and guiding the development of biocontrol strategies for sustainable agriculture.