Relative centrality of work (RCW) is defined as the psychological importance given by individuals regarding work relative to the importance they attach to other major domains of living. Prior evidence has been inconclusive in terms of how RCW might influence the life satisfaction (LS) of individuals. Hence, in this study, we hypothesize that this relationship is regulated by an individual’s current job features (job complexity [JC]) and national culture concerning work (performance orientation [PO]) independently and jointly. On the basis of representative samples of 23,622 employees from 33 nations, we find that the RCW–LS relationship is negative when JC is low. By contrast, high JC eliminates but does not reverse this negative trend. This two-way interaction only exists when employees simultaneously live in a nation whose culture stresses performance improvements and achievement of rewards from work, that is, nations with high PO. Although an individual’s national–cultural context does not moderate the RCW–LS linkage, it functions by making work relative to other life domains (RCW) and job characteristics (high JC) highly important in deriving satisfaction from one’s life.