Global change is expected to increase the arrival of opportunistic macroalgae, as well as the rate and extent of blooming events, causing severe negative impacts on marine and coastal ecosystems. Opportunistic macroalgae may represent a particularly interesting source of secondary metabolites, as they adapt to highly variable environments and have a withstanding capacity to cope with environmental stressors. Valorization could be a key solution to transform this huge biomass of opportunistic species into a potential for biotechnological and socioeconomic innovation. Before this, it is crucial to have a full understanding on how seasons, life stage and environmental variability modify their metabolome and thus, the quality of their biomass. In this regard, the holobiont perspective (relationship of macroalgae with their microbiome) is paramount to understand comprehensively the macroalgal ecophysiology and the environmental factors modulating their metabolome, all along their life-cycle until their degradation. HOLO-CWEED aims to study opportunistic macroalgae as holobionts to: 1) shed light on the opportunistic macroalgal ecophysiology, 2) assess the intrinsic (microbiome) and extrinsic (environment) factors affecting the quality of their metabolome along their life-cycle, and 3) assess the impact of massive macroalgal strandings on the surrounding seawater. This work will require an inter-disciplinary methodological approach gathering microscopy, biochemistry, metabolomics and metabarcoding, to have a complete understanding of macroalgal holobionts. The host institution facilities and expertise will be essential for stepping from fundamental research to applied research through the valorisation of macroalgae. HOLO-CWEED provides an original scientific approach to understand how opportunistic macroalgae thrive in a changing environment and assess how their massive degradation changes the seawater quality.