Accurate estimation of the postmortem interval (PMI) remains a major challenge in forensic science due to the complex and dynamic nature of decomposition. While postmortem biochemical and microbial alterations follow organised temporal patterns, their integrated behaviour under realistic conditions, particularly in the presence of prevalent xenobiotics, remains underexplored. Preliminary data support the relevance of Enterococcus faecalis as time-dependent indicators of PMI. Building on this, this project will use pathogen-free C57BL/6 mice to develop a multi-parametric framework for PMI estimation by integrating tissue-specific biochemical profiling with E. faecalis dynamics under exposure to relevant xenobiotics (cocaine, amoxicillin/clavulanic acid, and morphine). Biochemical analyses will be combined with culturomics to characterise microbial succession and its interaction with tissue degradation. The integration of these datasets will enable the development of predictive models for improved PMI estimation. This approach is expected to generate robust and informative biomarkers with potential translational applicability to human forensic contexts.