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Simple Summary: Difficulties in sensory processing are often found in neurodevelopmental disorders and can significantly impact how a child responds to and functions within their environment. Studies examining sensory processing in children with neurofibromatosis type 1 (NF1) are sparse. This cross-sectional study aims to address this gap by examining parent-reported sensory processing in a sample of 152 children with NF1. Approximately 61% of children with NF1 displayed differences in how they respond to sensory stimuli when compared to a typically developing control group. These difficulties were seen equally across ages and sex and were found to be associated with a higher degree of autistic behaviors, ADHD symptoms, lower adaptive skills, poorer social skills, and increased anxiety and affective symptoms. The results highlight the importance of accommodating multisensory processing difficulties at home and school when deciding how to support a child with NF1 across environments. Despite the evidence of elevated autistic behaviors and co-occurring neurodevelopmental difficulties in many children with neurofibromatosis type 1 (NF1), we have a limited understanding of the sensory processing challenges that may occur with the condition. This study examined the sensory profile of children and adolescents with NF1 and investigated the relationships between the sensory profiles and patient characteristics and neuropsychological functioning. The parent/caregivers of 152 children with NF1 and 96 typically developing children completed the Sensory Profile 2 (SP2), along with standardized questionnaires assessing autistic behaviors, ADHD symptoms, internalizing symptoms, adaptive functioning, and social skills. Intellectual functioning was also assessed. The SP2 data indicated elevated sensory processing problems in children with NF1 compared to typically developing children. Over 40% of children with NF1 displayed differences in sensory registration (missing sensory input) and were unusually sensitive to and unusually avoidant of sensory stimuli. Sixty percent of children with NF1 displayed difficulties in one or more sensory modalities. Elevated autistic behaviors and ADHD symptoms were associated with more severe sensory processing difficulties. This first detailed assessment of sensory processing, alongside other clinical features, in a relatively large cohort of children and adolescents with NF1 demonstrates the relationships between sensory processing differences and adaptive skills and behavior, as well as psychological well-being. Our characterization of the sensory profile within a genetic syndrome may help facilitate more targeted interventions to support overall functioning. [ABSTRACT FROM AUTHOR]