Electrospun scaffolds fabricated from poly(lactic-co-glycolic acid) (PLGA) have garnered widespread interest in biomedical applications due to their ability to mimic the extracellular matrix (ECM) structure with a tunable degradability profile. The properties of electrospun scaffolds are meticulously tailored for specific applications through the adjustment of polymer properties, solution parameters, and processing conditions. Solvent selection is crucial, influencing polymer spinnability and scaffold topographical, physical and mechanical features. Hansen solubility theory aids in predicting suitable solvent systems. The absence of specific data prompted a solubility experiment to determine Hansen solubility parameters for PLGA. Subsequently, various solvent systems were investigated for their impact on the microstructure of electrospun PLGA scaffolds. Optimizing the electrospinning process resulted in fibrous scaffolds with consistent average fibre diameter from different solvent systems, allowing a focused examination of the solvent's isolated influence on mechanical properties. PLGA samples electrospun using hexafluoro isopropanol (HFIP) displayed lower Young's modulus and ultimate tensile strength but higher failure strains than those created using binary solvent systems composed of tetrahydrofuran (THF), dichloromethane (DCM), and dimethylformamide (DMF). This research advances the understanding and optimization of electrospun PLGA scaffolds, enhancing their potential for biomedical applications.