With the proliferation of mobile devices characterizing modern cyber-physical systems, service switching and handoff over large coverage areas become key aspects of the Internet of Things (IoT), mainly when remotely controlling and interacting with mission-critical autonomous vehicles that potentially may cover quite large distances such as driverless cars and Unmanned Aerial Vehicles (UAVs). These requirements can now be fully satisfied by the widespread Fast handover for Proxy Mobile IPv6 (F-PMIPv6) technology, that can be yet considered as a cornerstone in emerging 5G communications, but, unfortunately, such an approach only supports homogeneous handover, that may result in a nontrivial problem due to the heterogeneity in mobile communications technologies characterizing the available cyber-physical solutions and IoT network access devices. Recently, many researchers developed efficient solutions for the integration of F-PMIPv6 and Media Independent Handover (MIH) to allow fast handover in a highly heterogeneous mobile network. However, these models lack the security features which are necessary to protect IoT devices during handoffs. In this paper, a new security protocol, MIH-based secure cross-layer handover protocol for Fast Proxy Mobile IPv6 networks (MIH-SPFP), is proposed, incorporating the features of Secure Protocol for Fast-PMIPv6 (SPFP) into F-PMIPv6-MIH and reducing the security risks during the handover. The proposed solution also provides low latency by reducing the re-authentication path during the inter-Mobile Access Gateway (MAG) handovers. The security of the proposed protocol has been analyzed by using Burrows–Abadi–Needham (BAN) logic and Automated Validation of Internet Security Protocols and Applications (AVISPA) tool and its performance has been evaluated through numerical simulation by selecting “Marathon Broadcasting” as a case study. Results show that the proposed protocol not only effectively secures the handover process but is also more efficient compared with the standard MIH handover solution.