Livestock occasionally face contamination incidents with lipophilic contaminants (e.g., PCBs, PCDD/Fs), breaking down the agro-food chain, and inducing social distress for farmers. Bovine meat has been found to be sensitive to such contamination risks. Indeed, two monitoring studies highlighted that more than 50% of the bovine meat samples from extensive farming systems exceeded either the action (product sale permitted, contamination source should be identified) or maximum (product sale prohibited, confiscation and incineration) regulatory levels. Understanding the fate of lipophilic contaminants in beef cattle is the cornerstone for a fair risk assessment. It is classically investigated via feeding experiments, from which feed-to-meat bioconcentration and biotransfer factors are computed. In such an approach, the animal system is seen as a ‘black box’ and the transfer factor is given as a single average value. Nonetheless, the rate of feed-to-meat transfer depends not only on contaminant physicochemical properties but also varies widely according to animal feeding and physiology. Aiming to go deeper into the understanding of the complex interplay between contaminant properties, lipid nutrition and animal physiology, an integrative and mechanistic approach should be developed. For such purpose, systemic modelling of the contaminant absorption, distribution, metabolism, and excretion (ADME) processes is the adequate media. Although fugacity-based or physiologically-based toxicokinetic (PBTK) models of lipophilic contaminant fate were previously developed for dairy cows, attempts in beef cattle are much scarcer. Bogdal et al. introduced a PBTK model describing PCBs and PCDD/Fs fate in suckling calf, whereas MacLachlan and Buhla described roughly weaned growing cattle with a generic one-compartment model. The aims were i) to set-up a mechanistic model describing the ADME of lipophilic contaminants in growing beef cattle and ii) to assess its suitability as a media to decipher the complex interplay between contaminant properties, lipid nutrition and animal physiology.