The goal of this study was to explore the influencing factors of pre-service science teachers' pedagogical content knowledge (PCK) for targeted aspects of nature of science (NOS) and nature of scientific inquiry (NOSI) in a 13-month teacher development program, through multiple data sources. The program included a research experience, a course on NOS/NOSI, and a teaching practicum. This was an exploratory multiple case study of two pre-service science teachers' (Rose and Charlie) experiences and development. Data were collected in multiple ways including open-ended surveys, interviews, observations, lesson plans, reflections, and teaching documents. All data were analyzed in three stages for coding, category generation, and emergent themes. Throughout the program, the two pre-service teachers improved their understanding of NOS/NOSI and successfully enacted their PCK for NOS and NOSI into their teaching of middle-level science topics. Rose and Charlie used their informed knowledge of the subject matter, instructional strategies, assessment, and curriculum towards teaching NOS and NOSI to engage students in making predictions, supporting claims with evidence, and reflecting on NOS/NOSI aspects relevant to their investigations. Some additional factors, such as teacher self-efficacy, lesson planning, or general pedagogical knowledge, appeared to impact their teaching practicum. This study provides a description of how pre-service science teachers can develop PCK for NOS and NOSI over time and transfer their understandings to teach NOS and NOSI.