Massive and recurrent strandings of pelagic Sargassum biomass have become the new norm in the Caribbean and the Western Africa since 2011, and there is no sign of this abating. These Sargassum events have negative environmental, socioeconomic and health impacts in the affected countries. In the meantime, various processing techniques and applications have been suggested for valorisation of this biomass. However, variability in quantity, quality and location creates substantial uncertainty for the development of reliable and robust industrial processes. As part of ongoing efforts to better characterise seasonal and geographical variations in the biochemical and elemental composition of the pelagic Sargassum biomass across the Caribbean, we analysed samples from Mexico, Jamaica and the Dominican Republic harvested during summer 2020 and winter 2021. Different degrees of variation were observed in the contents of ash, metals and metalloids, vitamins, fatty acids, amino acids and biogenic amines, and monosaccharides. Our results indicate that biomass is of highly variable quality depending on season and location. In this context, we suggest that biorefinery approaches geared towards controlled metal removal and focused on the extraction and purification of amino acids, fatty acids and vitamins should be prioritised to assess the potential valorisation of pelagic Sargassum biomass into standardised and high-value outputs.