In solar Organic Rankine Cycles (ORCs), the process directly influenced by solar radiation intensity and weather conditions. However, in many previous studies, the selection or design of working fluids has been performed based on fixed conditions, while the effect of collector outlet temperature variations on the nature of the optimal fluid has received less attention. In this study, a Computer-Aided Molecular Design (CAMD) framework was developed for the design of ORC working fluids at six hot source temperatures between 50oC and 200oC. The design problem was formulated and solved as a mixed-integer nonlinear programming (MINLP) model. In the proposed framework, molecular structural constraints, thermodynamic constraints, operational pressure limitations, and environmental and safety indicators including global warming potential, toxicity, flash point, and minimum ignition energy were considered. The turbine work output was defined as the primary objective function. The results demonstrated that variations in hot source temperature can lead to the design of two completely different fluids. For the low-temperature scenarios, a fluorinated hydrocarbon was identified as the optimal fluid, whereas for the high-temperature scenarios, a hydrocarbon was selected as the optimal candidate. Turbine power output varied between 1 and 51 kW, with significant shifts in operating conditions, including stream pressures and mass flow rates (ranging from 9 to 111 kmol/h). These findings indicate that the selection of working fluids for solar ORC systems should not be carried out independently of hot source temperature variations. Final fluid selection requires comprehensive process flexibility analysis, annual performance analysis, and property uncertainty assessment.