Background: In broiler chickens, the efficient utilization of macro- and micronutrients is influenced by various metabolic pathways that are closely linked to feed efficiency (FE), a critical metric in poultry industry, with residual feed intake (RFI) as the preferred proxy. Feed restriction is considered an approach to address the underlying molecular mechanisms of feed conversion. We hypothesized that broiler chickens with divergent RFI subjected to quantitative feed restriction differ in their pattern of molecular pathways for efficient nutrient utilization in liver as post-absorptive tissue. Methods: Cobb 500FF broiler chickens divergent for RFI (n = 112) were feed-restricted from day 9 until market weight at day 33–37 post-hatch. Based on a previous trial, feed restriction levels were set at 92% (low-RFI birds) and 80% (high-RFI birds) relative to the control groups. Transcriptomic analyses of the liver were conducted. Results: Due to the interaction of the RFI group and feeding regimen, a total of 140 to 507 differentially expressed genes were identified for the respective contrasts, with implications for hepatic metabolism and cellular stress response. Although the broilers did not realize their full growth potential under restrictive feeding (12.4% reduced body weight vs. controls, p = 0.094), the gene expression patterns indicate a lower susceptibility to blood coagulation (KNG1, FGG, and FGB), suggesting that controlled and mild feed restriction could lead to health benefits in less feed-efficient broilers. Moreover, FE traits are shown to be linked to cellular detoxification processes (MGST3 and CYP2AC2) and triacylglycerol syntheses (MOGAT1 and LPIN1). Conclusions: Divergent transcriptional profiles between broiler groups under varied caloric conditions indicate potential for optimizing nutritional management strategies.