In response to the increasing implementations of online problem-based learning (PBL), this paper presents a new framework, 4S PBL, with a wide range of strategies and technologies to empower instructors and learners. Based on a critical synthesis of research on and practice of PBL, self-regulated learning (SRL), socially shared regulated learning (SSRL), and related learning technologies, the 4S PBL framework outlines key strategies to address each of the four domains (i.e., motivation, affect, cognition and behaviors) at each PBL stage. A wide range of strategies is recommended with practical examples and research support. In addition, an array of learning technologies is discussed (e.g., asynchronous, synchronous, specialized, and emerging) with an emphasis on their proven or potential benefits in supporting online PBL. From multiple perspectives, the 4S PBL framework provides a solid foundation for educators and instructional design professionals to understand the complex dynamics of online PBL fully and empowers them with a pool of strategies and technologies accordingly. Similarly, online learners could leverage the strategies to develop their SRL and SSRL skills, collaborative learning, creative thinking, critical thinking, and problem-solving skills needed in the 21st century.