 This paper presents a novel methodology for optimizing the composition of perfluorocarbon nanomulsions, PFC and ES, to maximize their stability in fluorescence signal retention. This methodology utilizes multiple linear regression, MLR, to identify the optimal combination of PFC type and hydrocarbon concentration that results in the highest percentage diameter change, lowest polydispersity index, PDI, and least amount of fluorescence signal loss when loaded with curcumin, a known natural product with wide therapeutic potential. The optimized PFC NE is shown to have stable fluorescence even when loaded with curcumin, which is known to interfere with fluorescent dyes. This work demonstrates the utility of MLR and the development and optimization of fluorescent and theranostic PFC nanomulsions. This article was authored by Michelle Hernizzi and Yelena M. Janczyk.