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NLRP3 inflammasome is a vital component of the innate immune system, crucial in combatting pathogenic infections and responding to danger signals. At the same time, the aberrant activation of NLRP3 inflammasome is intricately linked with diseases such as diabetes, Alzheimer's disease, and lupus erythematosus. Therefore, regulation and intervention of inflammasome activation processes are pivotal for sustaining immune homeostasis and functionality. This review comprehensively summarizes recent progress in elucidating the regulatory mechanisms governing NLRP3 inflammasome activation, including post-translational modifications of NLRP3, interacting molecules, alterations in organelle and cellular localization, as well as metabolic processes and associated metabolites associated with NLRP3 function. Its objective is to offer novel perspectives on understanding inflammasome activation occurrences, inflammatory responses, and therapeutic approaches for inflammation-related disorders.