Although the concept of flow at work is increasingly receiving scholarly attention, knowledge about the interaction between challenge and hindrance stress demands in the context of flow is still lacking. Moreover, little is known about the stress-relieving capacity of coping mechanisms in connection to work-related flow. The aim of our study is to investigate whether and how challenge stress demands are related to work-related flow, and whether this relationship is moderated by a three-way interaction between challenge stress demands × hindrance stress demands × use of humor/cynicism. For this study we use survey data from 265 employees of a financial service organization in the Netherlands. Results clearly indicate a positive linear association between challenge demands and work-related flow and a negative association between hindrance demands and flow. Support is found for an interaction effect between challenge and hindrance stress demands, showing that hindrance demands weaken the positive association between challenge demands and work-related flow. Finally, cynicism is found to alter this relationship between work stress demands and work-related flow, increasing the negative effect of hindrance demands and confirming the expected three-way interaction. Results from this study have implications for the theory on work-related flow and advance the challenge-hindrance stressors framework. Insights from this study suggest that managers who wish to foster work-related flow should be alert to the use of cynicism among employees and address organizational issues that cultivate the negative attitude underlying this.