Controlling the particle size and its distribution is one of the crucial parameters to improve the hydrogel's efficacy in hemostasis and wound healing. To obtain an impressive and precise control of final particle size, it is essential to address a comprehensive evaluation. Cross-linked dextran microspheres' (CDMs) particle size behavior during the inverse suspension cross-linking process (SCP) was theoretically investigated. To carry out, a population balance approach was employed to predict the particle size and size distribution of CDMs in the SCP. Droplet breakage and coalescence rates equations were incorporated into the population balance equation (PBE) to simplify the PBE. Moreover, tunable parameters for this particular system were optimized using Genetic Algorithm (GA). After that, the impact of agitation rate as a key factor on final particle size evolution was modeled well. Finally, a superb accordance was observed between the modeling and empirical final particle size of CDMs with 50% dextran.