Due to the tunable optical absorption threshold and several intriguing physical properties, multiple-quantum-well (MQW) structures have been playing a crucial role in achieving ultra-high efficiency in tandem photovoltaic cells and various optoelectronic technologies. However, devices incorporating such nano-structures suffer from poor perpendicular carrier transport, which hinders device performance. On the other hand, designing MQWs is challenging. Simultaneously optimizing the structural parameters and constituent materials suggests a high design complexity with a large parameter space. In this report, on the basis of the quantitative analysis on the degradation of carrier transport, we propose a general design guideline for MQWs by which the structures and constituent materials can both be optimized targeting at a particular absorption threshold. We firstly demonstrate our design flow by optimizing an InGaP/InGaP strain-balanced (SB) MQW at 1.91 eV to replace In0.49Ga0.51P bulk serving as the top cell of dual-MQW triple-junction solar cells. Secondly, we apply the design concept to a conventional InGaAs/GaAsP SBMQW targeting at 1.23 eV, which is significant for not only high-efficiency single-junction photovoltaics but also current-matched tandem cells. The results illustrate the possibility of further improving current devices in terms of their constituent materials for QWs. Our design optimization method is considered to be applicable to any device based on QW structures.