Vibrio cholerae, a Gram-negative bacterium, is widely known as the cause of cholera, an acute diarrheal disease. While only certain strains are capable of causing cholera, non-O1/non-O139 V. cholerae strains (NOVC) can lead to non-pathogenic colonization or mild illnesses such as gastroenteritis. In immunocompromised patients, however, NOVC can cause severe infections, including rare cases of bacteremia, especially in those with underlying conditions like liver disease, hematologic disorders, and malignancies. This case report presents a rare instance of NOVC bacteremia in a 71-year-old patient with advanced lung cancer, illustrating the clinical presentation, diagnostic challenges, and treatment interventions required. The patient presented with fever, asthenia, and confusion, and was found to have bacteremia caused by NOVC, confirmed through blood cultures and molecular analysis. Treatment with intravenous ceftriaxone and ciprofloxacin led to a rapid clinical improvement and resolution of the infection. This case, along with an overview of similar incidents, underscores the importance of considering NOVC in differential diagnoses for immunocompromised patients presenting with fever, and highlights the necessity of timely diagnosis and targeted antimicrobial therapy to achieve favorable outcomes.