Low-power wide-area networks (LPWANs) demand high receiver sensitivity and efficient physical-layer signal processing. This paper introduces a unified framework for generalized block signal transmission in LPWANs, addressing the limitations of conventional symbol-by-symbol approaches. The framework comprises three key components: the signal block vector, the intra-block structure generator, and the signal basis matrix, and leverages quasi-orthogonal codewords formed through cyclically shifted spreading sequences. The resulting quasi-orthogonality enables reliable multi-user separation, particularly under asynchronous access. The framework establishes a conceptual foundation for block synchronization and provides a unified demodulation structure based on block correlation matching. It further supports flexible and systematic implementation, as demonstrated through applications to frequency-shift keying and chirp spread spectrum. This work advances scalable and efficient physical-layer design for next-generation LPWANs.