A novel methodology was implemented in the present study to concurrently control power conversion efficiency (η) and durability (D) of co-sensitized dye solar cells. Applying response surface methodology (RSM) and Desirability Function (DF), the main influential assembling (dye volume ratio and anti-aggregation agent concentration) and operational (performance temperature) parameters were systematically changed to probe their main and interactive effects on the η and D responses. Individual optimization based on RSM elucidated that D can be solely controlled by changing the ratio of vat-based organic photosensitizers, whereas η takes both effects of dye volume ratio and anti-aggregation concentration into account. Among the studied factors, the performance temperature played the most vital role in η and D regulation. In particular, however, multi-objective optimization by DF explored the degree to which one should be careful about manipulation of assembling and operational parameters in the way maximization of performance of a co-sensitized dye solar cell.