Iranian residential architecture, particularly during the Safavid era, manifests a profound interaction between nature and the Zeitgeist (spirit of the time)—a semantic bond that has been largely neglected in contemporary housing amidst changing modern lifestyles. This study aims to provide a comprehensive conceptual model of Iranian residential architecture, emphasizing the inherent relationship between the spirit of the time and nature as observed in the architecture of Muslim homes during the Safavid era, serving as a key paradigm within Islamic civilization. The research addresses three primary objectives: 1) elucidating the connection between nature and domestic architecture within Islamic thought; 2) identifying the unique Zeitgeist characterizing the Isfahan School; and 3) exploring how natural forms in Safavid dwellings correlate with this spirit of the time. The methodology is qualitative and descriptive-analytical, utilizing logical reasoning and case study analysis. Data collection synthesizes historical architectural documents, field observations, analysis of classical Persian paintings, and travelogues. Findings are synthesized through deduction and induction, ensuring a rigorous academic foundation. The results demonstrate that the Zeitgeist of the Isfahan School—structured around the components of ‘Transcendent Wisdom,’ ‘prominent masters and sages,’ ‘architectural systems,’ and ‘integrated architectural arts’—exhibits a profound and meaningful relationship with the ‘Spirit of Nature.’ This manifests in four key dimensions: the ‘unity of form, essence, and meaning,’ the ‘bond between form and essence,’ the ‘essence of nature,’ and the ‘meaning of nature,’ all articulated through 24 specific architectural indicators found in Safavid homes. ‘Transcendent Wisdom’ acts as the core mediator with all other elements. Ultimately, this conceptual model confirms that physical manifestations of nature in living spaces are intentionally designed to evoke deeper meanings, effectively realizing a unity-creating truth that harmonizes the diverse aspects of the domestic environment.