The liquid mixing process is an advantageous production method which has recently gained industrial interest for elaborating composites based on natural rubber (NR) and filler nanoparticles (NPs). Understanding how the relevant components such as polymer, fillers, as well as proteins and lipids coming from NR organize along the fabrication process is of importance for modulating material properties. Here, we successfully employed a combination of nano-imaging techniques to unravel the structure and evolution of hetero-aggregates formed by colloidal destabilization of a model NR latex - silica NPs liquid mixing process. First, field emission scanning electron microscopy (FESEM) was used to investigate the structures, from the early stage of contact between the particles until the formation of a composite. Results highlight an interaction in the liquid state between NR globules contained within the latex and silica NPs, hindering coalescence among globules. The latter can be achieved by applying shear in suspension or by solvent evaporation obtaining a dried composite. Atomic force microscopy coupled to infrared spectroscopy (AFM-IR) was employed to probe the in-depth nanoscopic distribution of silica NPs revealing a restricted mobility of the NPs during evaporation. Ultimately, the spatial distribution of proteins and lipids of NR, with respect to silica NPs, was investigated using dual color fluorescence images acquired with direct stochastic optical reconstruction microscopy (d-STORM) in a correlative light electron microscopy (CLEM) approach. The presence of silica NPs is found to influence the distribution of proteins and lipids in the composite; biomolecules form clusters of ~200 nm, which are partially colocalized with silica, highlighting an interaction between them. Our work provides comprehensive structural understanding of a model system undergoing liquid mixing, unlocking the potential of combining high-resolution imaging techniques to elucidate the structure of materials for tire applications.