Paper-based membraneless microfluidic fuel cell (PMMFC) has emerged as an alternative to conventional fuel cells. Extraction of optimum energy yield from these PMMFCs requires selection and study of various design and operating parameters. In this context, this paper presents reliability analysis and robust design of PMMFC composed of air-breathing graphite electrodes using multiple concentrations of formic acid and sulfuric acid as fuel and electrolyte, respectively. Combinations of four different grades of pencils are employed to prepare the electrodes using various pencil strokes. PMMFC is analyzed for two different orientations—horizontal and vertical, and the maximum power outputs were recorded. In order to analyze the combined effects of different factors governing the performance of PMMFC, a statistical approach of full factorial design is utilized to perform analysis of mean (ANOM), analysis of variance (ANOVA), signal to noise ratio (SNR), and desirability study. The response equations in terms of coded values of the factors are also derived. Rigorous desirability study, with the optimized parameters, concludes that the best desirability values for the horizontal and vertical arrangements of PMMFC are 0.8842 and 0.92768, respectively. Overall, this study helps to develop reliable, robust, and efficient PMMFC for many realistic applications.