Due to increasing the usage of membrane technology in pharmacy and biotechnology, controlling the morphology and achieving high-performance membranes is considered a significant issue in the membrane process. Rheological and thermodynamic properties are two main characteristics for tunning morphology. Therefore, in this research, the rheological and thermodynamic properties of polyethersulfone (PES) solutions N-methyl-2-pyrrolidone (NMP) and dimethylformamide (DMF) as two solvents are investigated. Rheological findings show that dope solution behaved differently in the presence of water and also polymer concentration alter the elastic behavior. Adding water to a dope solution of PES/DMF dominates elastic behavior which caused dense morphology whereas there are no significant changes in viscoelasticity of PES/NMP solution. Thermodynamic assessment of polymeric solutions and their phase diagram are other characteristics applied for precise prediction of structure and morphology. The findings of this research display that polymer concentration of 16wt% PES in NMP is the optimum dope formulation for constructing ultrafiltration membranes with a finger-like structure, more porosity, and better rejection of protein, 95.92%, than that of PES/DMF membrane (92.4%). The results prove that NMP is a suitable alternative to DMF as a solvent for PES ultrafiltration membranes owing to higher rejection of bovine serum albumin (BSA), hence NMP is chosen for further study of membrane morphology. To control and alter the structure of ultrafiltration membrane and better performance, effective parameters such as using organic and inorganic additive (citric acid and zinc oxide nanoparticle), coagulation bath composition, coagulation bath temperature, shear rate, and membrane thickness are investigated. Then, the effect of each parameter on membrane structure (porosity, mean pore size, specific surface, thickness, and hydrophilicity), performance (water Flux and protein rejection), and mechanical properties are evaluated. Among them, the shear rate has the greatest effect on protein rejection. Membranes derived with a shear rate of 172 s-1 have a porosity of about 89.2%, the highest Bovine serum albumin (BSA) rejection (99.4%), and water flux of 151.61????????2.?. The highest mechanical strength and maximum hydrophilicity are induced by the presence of zinc oxide nanoparticles as an additive. Furthermore. Membrane thickness has the lowest effect on water flux and protein rejection. The finding of this research displays that the design and processing parameters of membrane filtration have a significant role in the structure and an appropriate performance (high water flux and protein rejection). Keywords Ultrafiltration, phase separation, design and fabrication of membrane, protein separation