The traditional approaches to chemical risk assessment for human health are continuously challenged by their limitations, such as validity concerns, societal pressure to use animal-free methods, and resource constraints. New Approach Methodologies (NAMs) are considered a promising avenue toward modernisation of chemical risk assessment practices but their implementation in practice has been slow. This article aims to investigate the perspectives of human health risk assessors on the status quo, barriers and drivers of the acceptance and use of NAMs across different regulatory frameworks. A mixed method design was applied: qualitative interviews (N = 19) and an online survey with human health risk assessors from industry, regulatory agencies/institutions and academia (N = 222). The results show heterogeneity in familiarity and use of specific NAMs (e.g., QSARs as well-known and used vs. -omics approaches that are seldom used), the risk assessors' background (e.g., industry vs. regulatory agencies and institutions vs. academia) and the application context (e.g., screening/prioritisation vs. hazard identification/characterisation). The identified barriers and drivers offer pointers for the future integration and acceptance of NAMs in regulatory risk assessment. For instance, guidance documents can facilitate the use of NAMs, showcasing successful examples that increase trust in the methods and thus, the risk assessors' confidence in using these methods. Among other things, the article highlights the importance of considering human health risk assessors' needs and prerequisites to foster bottom-up coordinated efforts and to ensure the success of top-down legal and institutional change to incorporate NAMs in regulatory risk assessment.