To address the multifaceted aspects of indoor environmental sciences, this review paper critically investigates the optimization of thermal comfort and the development of heat-resilient indoor environments. Drawing on knowledge from a wide range of disciplines, such as chemistry, microbiology, public health, psychology, epidemiology, engineering, and toxicology, among others, it provides an extensive overview of recent study findings. The paper examines solutions targeted at reducing the negative impacts of heat stress while improving thermal comfort levels indoors, highlighting the complex link between indoor environment, human health, and comfort. Using both theoretical frameworks and actual data, the study assesses a variety of cutting-edge methods, such as behavioral interventions, heating, ventilation, and air conditioning (HVAC) systems, passive design strategies, and adaptable building materials. The statement underscores the importance of interdisciplinary cooperation in tackling the intricate problems related to interior thermal comfort and resistance to heat waves. The review attempts to offer practical insights for practitioners and researchers looking to optimize interior settings for human health and well-being by looking at the synergistic impacts of several treatments. Additionally, the research emphasizes how crucial it is to consider the larger context of climate change and its effects on interior spaces. To improve our understanding of thermal comfort optimization and heat-resilient design techniques, it suggests new research directions and knowledge gaps and advocates for ongoing interdisciplinary inquiry. In the end, the review adds to the continuing conversation about designing livable, sustainable, and healthful interior spaces in the face of changing weather patterns.