Fruit size is an important economic trait that is dependent both on genetic and environmental factors. Apple (Malus domestica Borkh) fruit has a unique structure where the fleshy part of the fruit (cortex) is derived largely from non-ovarian tissue while the core (pith) includes the true fruit derived from the ovary. In this study, we investigated the molecular and metabolic mechanisms regulating apple fruit development in a spatial and temporal manner. Results indicated that greater growth occurred in the cortex than the pith during fruit development due to more cell production and expansion. Targeted metabolite profiling revealed distinct characteristics C and N metabolism between the pith and cortex that may be associated with different growth patterns in different tissue. Variations of metabolic profiles were also revealed between early and mid/late fruit development. A subset of organ growth regulating genes have been identified and characterized in model species. The potential functions of organ growth regulating genes from five gene families were investigated in apple through analysis of their transcript abundance: Fruit Weight 2.2/Cell Number Regulator, Growth Regulating Factor (GRF), GRF-interacting Factor (GIF), ARGOS/ARGOS-Like and KLUH. These data indicate that MdGRF7a and MdGIF3 may act as positive regulators of cell production, while MdCNR5a may function as a negative regulator of cell production during fruit development in apple. RNA-seq analysis was performed to understand spatiotemporal and fruit load reduction-related changes in the transcriptome during fruit development. The cortex and pith displayed distinctive transcriptome profiles during all three stages analyzed: cell production, transition from cell production, and cell expansion. Weighted gene co-expression network analysis (WGCNA) revealed a negative regulator of cell production: TEOSINTE BRANCHED 1/CYCLOIDEA/PROLIFERATING CELL NUCLEAR ANTIGEN FACTOR1 (TCP). Transcript accumulation pattern of this transcription factor was consistent with negative regulation of spatiotemporal cell production patterns in the developing fruit. A regulatory cascade involving several miRNAs and this TCP has been previously implicated in the regulation of cell production during Arabidopsis leaf growth. Data presented here are consistent with a similar role for components of this cascade in regulating cell production during apple fruit growth.