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Abstract As one of the noninvasive screening and diagnostic tools for human breath monitoring of various diseases, chemiresistive devices with nanomaterials as the sensing interfaces for detecting volatile organic compounds (VOCs) have attracted increasing interests. A key challenge for the practical applications is an effective integration of all components in a system level. By integrating with the system components, it provides reliable and rapid results as a fast‐screening method for healthcare, safety, and environmental monitoring. This paper highlights some of the latest developments in chemiresistive sensors designed for the detection of VOCs and human breaths. It begins with a brief introduction to the fundamental principles of chemiresistive sensors with nanoparticle‐structured sensing interfaces. This is followed by a discussion of the recent fabrication methods, with an emphasis on nanostructured materials. Some of the recent examples will be highlighted in terms of recent innovative approaches to sensor applications and system integrations. Challenges and opportunities will also be discussed for the advancement and refinement of the chemiresistive sensor technologies in breath screening and monitoring of diseases.