Monkeypox infections in the US and across the world have been rising in the past few months. Most of these infections have been found to be transmitted among men who have sex with men (MSM). Our case report discusses the rare presentation of a patient with monkeypox along with multiple comorbidities, including AIDS, late latent syphilis, acute hepatitis C, and asymptomatic and scrotal and penile cellulitis secondary to MRSA. Further, our case report raises discussion on the need for further research to identify the effect of monkeypox vaccine on symptomatic patients who are immunocompromised.