The liver is a metabolically adaptable organ that is essential for controlling blood glucose and cholesterol levels. Fatty acids (FAs) are continuously flowing into the liver from a variety of sources, such as dietary sources, adipose tissue, endogenous synthesis from non-lipid precursors, intrahepatic lipid droplets, and recycling of triglyceride-rich leftovers. Triglycerides, which can be oxidised, stored, or released into the bloodstream as very low-density lipoproteins, are produced in the liver using FAs. Many factors can influence intrahepatic FA partitioning, and while there is good evidence that both phenotype (e.g., sex, ethnicity, and adiposity) and dietary macronutrient composition can play a role in intrahepatic triglyceride accumulation, their interaction is still poorly understood. The processes of FA uptake, FA synthesis, and the intracellular partitioning of FAs into storage, oxidation, or secretory pathways are tightly regulated; an imbalance in these processes leads to intrahepatic triglyceride accumulation and is linked to the development of metabolic dysfunction-associated steatotic liver disease. This review's objectives are to investigate how phenotypes affect the delivery, synthesis, and disposal of FAs and to comprehend how the makeup of dietary macronutrients may affect how FAs are partitioned in the human liver in vivo.