The use of phototherapy as an adjuvant bladder cancer treatment has long been considered, but its application has been severely hampered due to a lack of tumor specificity, unpredicted cytotoxicity, and insufficient anticancer efficacy. In this study, we aim to manufacture anti-EGFR indocyanine green (ICG) mitomycin C (MMC) encapsulated perfluorocarbon double nanoemulsions (EIMPDNEs), and explore their photochemotherapeutic efficacy on EGFR-expressing bladder cancer cells in vitro. The EIMPDNEs were manufactured using a double emulsification technique followed by antibody conjugation on the particles’ surfaces. The EIMPDNE were 257 ± 19.4 nm in size, with a surface charge of −12.3 ± 2.33 mV. The EGFR targetability of the EIMPNDE was confirmed by its enhanced binding efficiency to T24 cells when compared with the performance of nanodroplets without EGFR conjugation (p < 0.05). In comparison with freely dissolved ICG, the EIMPDNEs with equal ICG content conferred an improved thermal stability to the encapsulated ICG, and were able to provide a comparable hyperthermia effect and significantly enhanced the production of singlet oxygen under 808 nm near infrared (NIR) exposure with an intensity of 6 W cm−2 for 5 min (p < 0.05). Based on viability analyses, our data showed that the EIMPDNEs were effective in bladder cancer cell eradication upon NIR exposure (808 nm; 6 W cm−2), and the resulting cell death rate was even higher than that caused by a five-fold higher amount of entrapped MMC alone. With the merits of improved ICG stability, EGFR binding specificity, and effective cancer cell eradication, the EIMPDNEs exhibit potential for use in EGFR-expressing bladder cancer therapy with lower chemotoxicity.