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• Thermal-mechanical performance of the hottest pin under MYRRHA irradiation loaded with homogeneous Am-bearing fuels. • Consideration of both In-Pile test Section and driver irradiation scenarios associated to the latest "Revision 1.8" MYRRHA design. • Derivation and application of a surrogate model for He production in MYRRHA Am-MOX. • Evaluation of the compliance with safety limits under both IPS and driver irradiation. • Sensitivity analysis to identify the impact of the Am content compared to other parameters / phenomena relevant to the pin performance. Minor actinides are the main contributors to medium- and long-term radiotoxicity and heat production in spent nuclear fuels. Research efforts are currently ongoing to explore different options to dispose of such radionuclides, e.g., their burning in fast reactors within mixed-oxide fuels. The MYRRHA sub-critical reactor is one of the future facilities with envisaged burning and transmutation capabilities. This work assesses the thermal–mechanical performance of a homogeneous Am-bearing fuel pin both in the In-Pile test Section position of the MYRRHA "Revision 1.8" core and under driver irradiation. The normal operating conditions of MYRRHA are considered, with a focus on the safety design limits and involving sensitivity analyses to evaluate the impact of increasing americium contents (in the range 0–5 wt%) on safety-relevant simulation outcomes. The simulations are performed with the TRANSURANUS fuel performance code (version v1m4j22) coupled with the SCIANTIX physics-based module for inert gas behaviour, and rely on a dedicated surrogate model for the helium source term during MYRRHA irradiation accounting for the relevant contribution of the fuel americium enrichment, besides advanced models for the properties and behaviour of the specific pin materials. The analyses reveal the suitability and safety under irradiation of MOX fuels with low Am enrichments according to the current MYRRHA design. [ABSTRACT FROM AUTHOR]