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In this paper, state-of-the-art collector-up (C-up) heterojunction bipolar transistors (HBTs) with different thermal-via structures (TVS) have been systematically investigated by an enhanced genetic-algorithm (GA) approach. According to recent literature, C-up HBTs are compelling candidates as active components integrated in modern power amplifiers (PAs). To meet the immense demand for miniature PAs in advanced mobile phones, the temperature profiles of multi-finger C-up HBTs with TVS has been described. The thermal coupling between collector fingers as well as various finger pitches and the size effect on the maximum operation temperature within the transistor have been scrutinized. In addition, the thermal management and packaging design of the device has been optimized using a highly efficient GA combined with fuzzy-logic technique. The proposed analysis methodology is demonstrated on the potential InGaP/GaAs C-up HBT. An elucidation of actually-measured, finite-element-calculated, and globally-optimized results has been presented. Evaluated from this effective simulation tool and in comparison with prior works, the remarkable improvements show that the thickness of the TVS can be further reduced by more than 35%, and the thermal resistance of the transistors can be greatly improved over 45%. As a result, it is revealed that the significant thermal performance can be achieved with a highly-compact packaging design, and the thermally stable InGaP/GaAs C-up HBT should be viable for the implementation in the next-generation handset PAs.