Tuberculosis (TB): This is often considered the most likely diagnosis for drenching night sweats and unintentional weight loss, especially in regions with high TB prevalence. TB can cause systemic symptoms including fever, night sweats, weight loss, and fatigue.

Lymphoma: Both Hodgkin's and non-Hodgkin's lymphoma can present with systemic symptoms such as night sweats, fever, and unintentional weight loss. These symptoms are part of the B symptoms used in staging lymphoma.
Chronic Infections (e.g., Endocarditis, Osteomyelitis): Chronic infections can lead to prolonged fever, night sweats, and weight loss due to the body's ongoing inflammatory response.
Chronic Malignancies (e.g., Lung, Pancreatic Cancer): Various cancers can cause weight loss and night sweats, either due to the tumor itself or due to paraneoplastic syndromes.

HIV/AIDS: Although less common, HIV infection can present with night sweats and weight loss, particularly in the later stages. Missing this diagnosis could lead to delayed treatment and significant morbidity.
Pheochromocytoma: A rare tumor of the adrenal gland that can cause episodic hypertension, sweating (including night sweats), and weight loss. It's crucial to diagnose this condition due to its potential for severe cardiovascular complications.
Hyperthyroidism: Can cause weight loss and sweating, including night sweats, due to the increased metabolic rate.

Brucellosis: A zoonotic infection that can cause fever, night sweats, and weight loss, among other symptoms. It's rare in many parts of the world but should be considered in individuals with exposure to infected animals.
Whipple's Disease: A rare, systemic bacterial infection that can cause weight loss, fever, and night sweats, along with gastrointestinal and neurological symptoms.
Castleman Disease: A rare disorder that involves an overgrowth of cells in the body's lymph nodes, which can lead to systemic symptoms including fever, night sweats, and weight loss.