Background/Objectives: Nurses play a key role in supporting patient adherence to biosimilars, a responsibility that depends on their knowledge and understanding of biological therapies. This study aimed to assess nurses’ knowledge and attitudes toward biosimilars in Spain and to examine the demographic and professional factors that shape them. Methods: A self‑administered, web‑based survey was distributed in Spain between May and June 2024 to evaluate registered nurses’ knowledge and attitudes toward biosimilars. Associations were explored using Spearman’s correlation and Fisher’s exact tests, and predictors were examined through ordinal regression models. Results: A total of 402 nurses responded. 63.7% reported at least basic knowledge of biosimilars. Access to industry‑led training was strongly associated with higher knowledge levels (OR = 11.256; p < .001), whereas lack of awareness of biosimilar use in the workplace was associated with lower knowledge (OR = 0.176; p < .001). Nurses’ confidence in the safety and efficacy of biosimilars increased with knowledge level—from basic (OR = 3.823; p < .001) to intermediate (OR = 4.747; p < .001) and advanced (OR = 14.594; p < .001). Confidence was also greater among nurses working with biosimilars in their units (OR = 3.959; p = .004) and those in hospital ambulatory care services (OR = 2.506; p = .022). Conclusions: Nurses in Spain predominantly demonstrate basic knowledge of biosimilars, emphasizing the need for broader access to training. industry‑led courses emerged as the most relevant modifiable factor for improving both knowledge and confidence. Strengthening collaboration with the pharmaceutical industry may support informed clinical practice and improve patient adherence to biosimilar therapy.

Background/Objectives: Nurses play a key role in supporting patient adherence to biosimilars, which requires adequate knowledge of biological therapies. This study aimed to assess nurses’ knowledge and attitudes toward biosimilars in Spain, representing the first nationwide assessment of Spanish nurses’ knowledge and predictive determinants of reliance on biosimilars. Methods: A self-administered, web-based survey was distributed between May and June 2024. Associations were explored using Spearman’s correlation and Fisher’s exact tests, and predictors were examined with ordinal regression models. Results: A total of 402 nurses responded. Most (63.7%) reported at least basic knowledge of biosimilars. Access to industry-led training was strongly associated with higher knowledge (OR = 11.256; p < 0.001), while lack of awareness of workplace biosimilar use was linked to lower knowledge (OR = 0.176; p < 0.001). Confidence in biosimilar safety and efficacy increased with knowledge level (ORs 3.823–14.594; all p < 0.001) and was higher among nurses working with biosimilars in their units (OR = 3.959; p = 0.004) and in hospital ambulatory care services (OR = 2.506; p = 0.022). Conclusions: Spanish nurses predominantly demonstrate basic knowledge of biosimilars, highlighting the need for broader training access. Industry-led training was the strongest modifiable factor to improve knowledge and confidence. Strengthening collaboration with the pharmaceutical industry may support informed practice and enhance patient adherence to biosimilar therapy.