Introduction <p>Postnatal CMV infection (pCMV) acquired via breastmilk is associated with morbidity and mortality in vulnerable infants (&lt;32 weeks or &lt;1500 g). ‘Treatment’ of breast milk reduces CMV infectivity but quantitative impact on transmission, viral loads, bioactive and nutritional elements is unknown. We conducted a systematic review and meta-analysis to assess how each method impacts CMV transmission rates and viral loads and provide a narrative review of their impact on nutritional and bioactive elements.</p> Methods <p>Three search strategies for MEDLINE and EMBASE were used to identify articles studying the impact of treatment methods on CMV transmission (Arm A), nutritional elements (Arm B) and bioactive elements (Arm C). Two authors independently screened articles against inclusion and exclusion criteria. Included articles underwent quality assessment using the ROBINS-I tool. Quantitative analysis of data extracted from arm A is presented, alongside narrative reviews of arms B and C.</p> Results <p>Twenty-six studies (<i>n</i> = 3024 infants) were included for arm A. Heat treatment methods and freeze thawing resulted in 82% and 53% reduction CMV transmission respectively, compared to untreated milk. Correlation between viral load magnitude and transmission risk was not significant. Macronutrients remained largely stable after treatment, but bioactive elements were significantly degraded by heat treatment methods. High Pressure Processing was significantly better at preserving bioactive elements compared to heat treatment.</p> Conclusion <p>Heat treatment is most effective in reducing CMV infectivity in breastmilk but is associated with higher degradation of bioactive elements, whilst microwave irradiation and HPP eliminate CMV in breastmilk and preserve its immunological integrity.</p>