For software iSCSI initiators, without additional configuration the default behavior for iSCSI pathing is for ESXi to leverage its routing tables to identify a path to its configured iSCSI targets. Without solid understanding of network configuration and routing behaviors, this can lead to unpredictable pathing and/or path unavailability in a hardware failure. To configure predictable and reliable path selection and failover it is necessary to configure iSCSI port binding (iSCSI multipathing).
Configuration and detailed discussion are out of the scope of this document, but it is recommended to read through the VMware document that describes this and other concepts in-depth.
BEST PRACTICE: Use Port Binding for ESXi software iSCSI adapters when possible.
Note that ESXi 6.5 has expanded support for port binding and features such as iSCSI routing (though the use of iSCSI routing is not usually recommended) and multiple subnets. Refer to ESXi 6.5 release notes for more information.