Syntactic foams with fly ash cenospheres or commercial microballoons as fillers have been widely used in various applications ranging from aerospace to marine fields and the automotive industry. However, these two extensively adopted fillers possess multiple shortcomings, such as variations in the composition, material degeneration and distinct structural heterogeneity, which will inevitably hamper accurate prediction of the structure-property relationship and the corresponding design of the syntactic foams, reducing material utilization. Here, we present a microfluidic-based approach integrated with a subsequent heat treatment process to engineer syntactic foam fillers with a predefined composition, specified dimensional scope and reduced structural heterogeneity. These fillers are fully guaranteed by the synergy of the flexible and controllable generation of droplet templates with hydrodynamic regulation and rational selection of the nanoparticle dynamic response with respect to the heating temperature. In addition, two distinct surface morphologies have been observed with a temperature demarcation point of 1473 K, further endowing the fillers with multiplicity and optionality, simultaneously laying the foundation to regulate the properties of the syntactic foams through the diversity of the filler selection. Then, we fabricated a syntactic foam specimen by mold casting, and the integrity of the fillers inside was verified using an elaborate buoyancy comparison experiment, exhibiting its potential value in lightweight related applications. As the fillers derived from our approach show significant advantages over conventional ones, they will provide considerable benefits for the regulation and improvement of syntactic foam fillers in many practical applications.