Simple Summary: According to the literature, 35–71% of multiple myeloma patients have nutritional disorders. In the development of cachexia and malnutrition, the inflammatory process, accompanied by an increase in the level of proinflammatory cytokines, plays a key role. Interleukin-1β is a cytokine that plays an important role in the mechanisms responsible for muscle and adipose tissue breakdown during malnutrition and cachexia. This study aimed to investigate the association of IL1B gene polymorphism and interleukin-1β plasma concentration with the occurrence of nutritional disorders and survival in patients with multiple myeloma. The presence of the CC genotype of the IL1B gene was associated with a higher plasma concentration of interleukin-1β, a higher risk of cachexia, and poor prognosis. Determination of IL1B polymorphism may be a useful predictive marker of the risk of cachexia and prognostic factor in multiple myeloma patients. Background: Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35–71% of MM patients. Interleukin 1 beta (IL-1β) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1β in the assessment of the risk of nutritional disorders and prognosis in patients with MM. Methods: In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1β ELISA kit was used to determine IL-1β concentration in plasma samples. Results: Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1β in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1β plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). Conclusions: Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1β may be useful in the assessment of the risk of cachexia and prognosis in patients with MM. [ABSTRACT FROM AUTHOR]