This article presents a wide-dynamic-range multi-sensor readout interface for portable environmental monitoring systems with two-step self-optimization schemes. It proposes two-step self-optimization methods of adaptive range detection and coarse self-cancelation (CSC) for current-type sensor interfaces, and range-based path control and current DAC-based correlated double sampling (CDS) for resistive sensing interfaces. Their digital conversions are provided by two kinds of high-resolution ADCs, namely, an incremental ΔΣ current detector and a two-step SAR- ΔΣ ADC. The proposed ROIC prototype is fabricated in a 180-nm CMOS process, achieving a dynamic range (DR) of 136.5 dB and 160.9 dB, and a maximum SNR of 109.8 dB and 108.6 dB for current and resistance detection, respectively. For system-level feasibility, an environmental monitoring system prototype based on the ROIC is also manufactured and functionally verified by integrating two kinds of in-house micro-electro-mechanical systems (MEMS) sensor devices, the MCU, and the Bluetooth module, supporting wireless air quality and water pollution monitoring capabilities.