PURPOSE: There is a wide range of individual and work environment factors that influence work ability among workers with pain and stress-related ill-health. The multiple interactions and overlap between these factors are insufficiently understood, and a network approach could mitigate limitations of previous research. This pilot study aimed to explore interactions between individual characteristics and psychosocial work environment and potential links to long-term work ability. METHODS: Prospective data from a prevention project was used. Individuals (N = 147) with pain and/or stress-related ill-health (95% women) at public sector workplaces filled out baseline questionnaires about a collection of individual and work environment factors, which were used for constructing undirected networks. The model was run in three subsamples of workplaces. Finally, a separate model was established with work ability at 6-month follow-up as outcome variable. A shortest pathway analysis was calculated to identify mediators of work ability. RESULTS: Symptom catastrophizing and perceived stress were the most influential factors in all network models. Symptom catastrophizing and pain-disability risk were found to mediate the relation between perceived stress and long-term work ability. Further, demand-control-support factors were interrelated, and patterns of interaction differed between different types of workplaces. CONCLUSION: The findings support the importance of individual factors, specifically symptom catastrophizing in an individual's coping with pain or stress-problems and its influence on long-term work ability. Catastrophizing might play a role in stress-related disorders which should be further investigated. Individual and work environment factors interact and vary across context, which needs to be taken into consideration to prevent pain and stress-related ill-health at work.