Polysaccharide-nanoparticle (NP) hybrid nanoclusters have great potential to revitalize diverse bioapplications; however, fabricating polysaccharide-based hybrid nanoclusters composed of high-quality NPs generated in the organic phase remains a challenge. Here, using calcium alginate as a polysaccharide/tetramethylammonium hydroxide (TMAOH) combination, we report a novel approach to the design of alginate-hydrophobic magnetic-plasmonic core-shell (MPCS) NP hybrid nanoclusters (A-MPCS HNCs). Furthermore, we observe the dependence of the formation of A-MPCS HNCs on the TMAOH concentration. The enhanced performance in both magnetic resonance r(2) relaxivity and photoacoustic (PA) signals and the biocompatibility/bioactivity as well as the in vivo performance of A-MPCS HNCs shows them to be a promising magnetic resonance/photoacoustic dual-mode imaging agent. Our strategy could open doors to the use of other precious high quality nanomaterials created in the organic phase via well-established synthetic chemistry in the. design of alginate-hydrophobic nanomaterial hybrid nanoclusters, giving rise to novel and multifarious bioapplications.