Dense-array concentrating photovoltaic (DA-CPV) systems suffer from power generation limits due to extreme operation conditions. This study primarily aims to analyze the multi-physics effects of various optical, electrical, and thermal conditions on the performance of DA-CPV systems. Different module configurations are employed in the simulations to evaluate the coupling impacts of changing illumination distributions and temperature profiles on the system performance. The results demonstrate that module configurations have significant influence on the output power and temperature contour of DA-CPV modules. Compared with conventional total-cross-tied connections, decrements of average module temperature and central module temperature by at least 5 and 12 °C, respectively, and increment of output power by at least 48.29% are achieved based on the quartered rotational symmetry (QRS) connection. Under various non-uniform illuminations, the maximum power will be obtained at anti-Gaussian temperature profiles. Compared with the uniform and Gaussian temperature profiles, the inverse Gaussian profiles can further improve the module output power by at most 1%. Meanwhile, relying on the achieved correlation between the optimized temperature profiles and illumination shapes for the CPV module with the QRS connection, the output performance of the CPV module under various raidation intensities is evaluated. In the range of 100–1200 W/m2 of solar radiation, more than 99.7% of the maximum module power is maintained with the optimized anti-Gaussian temperature profile.