Papaya (Carica papaya L.) is a principal horticultural crop of tropical and subtropical regions. Knowledge of how papaya responds to environmental factors provides a scientific basis for the development of management strategies to optimize fruit yield and quality. A better understanding of genotypic responses to specific environmental factors will contribute to efficient agricultural zoning and papaya breeding programs. The objective of this review is to present current research knowledge related to the effect of environmental factors and their interaction with the photosynthetic process and whole-plant physiology. This review demonstrates that environmental factors such as light, wind, soil chemical and physical characteristics, temperature, soil water, relative humidity, and biotic factors such as mycorrhizal fungi and genotype profoundly affect the productivity and physiology of papaya. An understanding of the environmental factors and their interaction with physiological processes is extremely important for economically sustainable production in the nursery or in the field. With improved, science-based management, growers will optimize photosynthetic carbon assimilation and increase papaya fruit productivity and quality.