The coming decades will see a substantial increase in the population of older adults, accompanied by significant demographic and family structure changes worldwide. As a result, the empty nest period—the postparental phase in parents’ lives when their children have left home and they are no longer engaged in childrearing—is becoming an increasingly common experience in Western and Asian cultures. The current theoretical review examines the psychological consequences of the empty nest period on loneliness and well-being across cultures, emphasizing the impact of cultural factors on these experiences. By synthesizing research from Western and Asian contexts, we explore two primary theoretical mechanisms—role loss and role strain relief—that shape the postparental phase’s psychological outcomes. Our review reveals that while some parents experience reduced well-being due to role loss, others benefit from role strain relief and increased social engagement. We highlight how cultural differences in familial roles, gender roles, social expectations regarding nest-leaving, and social participation patterns moderate these mechanisms. We propose a comprehensive cultural framework, along with a discussion of culturally sensitive interventions to enhance the well-being of empty nesters globally.